Cardiac resynchronization therapy optimization based on intracardiac impedance and heart sounds

0001This application is a continuation of U.S. patent application Ser. No. 14/158,533, filed on Jan. 17, 2014 now issued as U.S. Pat. No. 9,387,330), which is incorporated herein by reference in its entirety.

0002The disclosure herein relates to methods for optimizing device parameters for delivering therapy to a patient's heart (e.g., paced AV and VV delay for cardiac resynchronization therapy (CRT)), for example, using intracardiac impedance signals, heart sounds, etc., and further to apparatus for performing such processes.

0003Cardiac resynchronization therapy has been clinically demonstrated to improve cardiac function in patients suffering from various cardiac conditions such as congestive heart failure. CRT may apply electrical stimulation, or pacing, to one or both ventricles and/or atria to improve cardiac chamber coordination, which in turn, may improve stroke volume, pumping efficiency, etc. The time interval between pacing the atria and the ventricles may be referred to as the AV delay and the time interval between pacing each of the ventricles may be referred to as the VV delay.

0004For example, CRT for heart failure (HF) patients has been shown to improve hemodynamic parameters, physical capacity, long-term quality of life, and reduce mortality and morbidity. For successful resynchronization to occur, the atrioventricular delay (AV delay) and interventricular delay (VV delay) may be optimized. Methods to optimize these parametric delays have been explored with various sensing mechanisms such as electrocardiography (ECG), electrograms (EGMs), arterial blood pressure and cutaneous impedance, and subsequently compared to the echocardiography (e.g., ultrasound) optimization method. However, echo optimization methods for CRT are often subjective and show high intra- and inter-individual variability.

0005CRT systems having automated selection of AV and VV delays without clinician intervention exist. For example, systems that automatically adjust AV and VV delays may be generally disclosed in U.S. Pat. No. 6,223,082 issued to Bakels, et al., U.S. Pat. No. 7,548,784 issued to Chinchoy, and U.S. Pat. No. 7,228,174 to Burnes, et al., each of which are incorporated herein by reference in their entirety.

0006Impedance sensors have been used in pacing systems for obtaining information associated with cardiac function. For example, U.S. Pat. No. 5,501,702 issued to Plicchi, et al. and U.S. App. Pub. No 2009/0275854 A1 to Zielinski et al., each of which are incorporated herein by reference in their entirety, discloses measuring impedance using various electrode combinations.

SUMMARY

0007The disclosure herein relates to methods to measure hemodynamic parameters with an implanted device using sensors, such as, for example, intracardiac impedance in combination with heart auscultations to assist in CRT optimization. For example, intracardiac impedance measurements made based on temporal fiducial points associated with the systolic and/or diastolic portions of the cardiac cycle (e.g., fiducial points acquired using heart sounds, impedance minimums and maximums, R-R intervals, etc.) may be used to optimize one or more device parameters (e.g., AV delay, VV delay, etc.).

0008One exemplary implantable medical device disclosed herein for use in delivering CRT to a patient's heart, wherein the cardiac resynchronization therapy is delivered based on a plurality of device parameters, may include a sensing module configured to monitor at least an intracardiac impedance between at least two electrodes to provide an intracardiac impedance signal, a therapy delivery module configured to deliver cardiac therapy to the patient's heart, and a control module coupled to the sensing module and the therapy delivery module and configured to: deliver cardiac resynchronization therapy to a patient at a plurality of options for at least one of the device parameters (e.g., a plurality of paced A-V delays, a plurality of paced V-V delays, a plurality of pacing sites, a plurality of pacing vectors, a plurality of locations for lead placement, etc.) and acquire selection data relating to each of the plurality of options for the at least one device parameter for at least one cardiac cycle. Acquiring the selection data at each of the plurality of options of the device parameter may include: acquiring temporal fiducial points associated with at least a part of a systolic portion of at least one cardiac cycle and temporal fiducial points associated with at least a part of a diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations; acquiring, at each of the plurality of electrode vector configurations and about simultaneously with the acquired fiducial points, an intracardiac impedance signal; extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based on the temporal fiducial points and associated with the systolic portion of at least one cardiac cycle and associated with the diastolic portion of the at least one cardiac cycle; and determining selection data for each of the plurality of electrode vector configurations based on the extracted measurements. The control module may be further configured to use the acquired selection data relating to each of the plurality of options of the device parameter to set one option of the plurality of options for delivery of cardiac resynchronization therapy to the patient's heart.

0009One exemplary implantable medical device method for delivering cardiac resynchronization therapy to a patient's heart (e.g., wherein the cardiac resynchronization therapy is delivered based on a plurality of device parameters) may include delivering cardiac resynchronization therapy to a patient at a plurality of options for at least one of the device parameters; acquiring selection data relating to each of the plurality of options for the at least one device parameter for at least one cardiac cycle (e.g., wherein acquiring the selection data at each of the plurality of options of the device parameter may include acquiring temporal fiducial points associated with at least part of a systolic portion of at least one cardiac cycle and temporal fiducial points associated with at least part of a diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations, acquiring, at each of the plurality of electrode vector configurations and about simultaneously with the acquired fiducial points of the systolic portion and the diastolic portion of the at least one cardiac cycle, an intracardiac impedance signal, extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based on the temporal fiducial points and associated with the systolic portion of at least one cardiac cycle and associated with the diastolic portion of the at least one cardiac cycle, and determining selection data for each of the plurality of electrode vector configurations based on the extracted measurements); and using the acquired selection data relating to each of the plurality of options of the device parameter to set one option of the plurality of options for delivery of cardiac resynchronization therapy to the patient.

0010Another exemplary implantable medical device for use in delivering therapy to a patient's heart may include a sensing module configured to monitor an intracardiac impedance between at least two electrodes to provide an intracardiac impedance signal and to monitor heart sounds of a patient (e.g., sensed heart sounds may be representative of mitral valve closure and aortic valve closure); a therapy delivery module configured to deliver cardiac resynchronization therapy to the patient's heart; and a control module coupled to the sensing module and the therapy delivery module and configured to acquire selection data relating to each of a plurality of paced conduction delays (e.g., at least one of a plurality of paced A-V delays and a plurality of paced V-V delays) for at least one cardiac cycle (e.g., wherein acquiring the selection data at each paced conduction delay may include sensing heart sounds defining temporal fiducial points associated with at least a diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations, acquiring, at each of the plurality of electrode vector configurations and about simultaneously with the sensed heart sounds, an intracardiac impedance signal, extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based at least in part on the defined temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle, and determining selection data for each of the plurality of electrode vector configurations based on the extracted measurements); and use the acquired selection data relating to each of the plurality of conduction delays to set one conduction delay of the plurality of conduction delays for delivery of cardiac resynchronization therapy to the patient.

0011Another exemplary implantable medical device method may include delivering cardiac resynchronization therapy to a patient at a plurality of paced conduction delays; acquiring selection data relating to each of the plurality of paced conduction delays for at least one cardiac cycle (e.g., wherein acquiring the selection data at each paced conduction delay may include sensing heart sounds defining temporal fiducial points associated with at least a diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations, acquiring, at each of the plurality of electrode vector configurations and about simultaneously with the sensed heart sounds, an intracardiac impedance signal, extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based at least in part on the defined temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle, and determining selection data for each of the plurality of electrode vector configurations based on the intracardiac impedance measurements); and using the acquired selection data relating to each of the plurality of conduction delays to set one conduction delay of the plurality of conduction delays for delivery of cardiac resynchronization therapy to the patient.

0012Another exemplary implantable medical device for use in delivering therapy to a patient's heart may include a sensing module configured to monitor an intracardiac impedance between at least two electrodes to provide an intracardiac impedance signal and to monitor heart sounds of a patient; a therapy delivery module configured to deliver cardiac therapy to the patient's heart; and a control module coupled to the sensing module and the therapy delivery module and configured to control delivery of cardiac resynchronization therapy to a patient at a plurality of paced conduction delays, acquire selection data relating to each of the plurality of paced conduction delays for at least one cardiac cycle (e.g., wherein acquiring selection data may include sensing heart sounds defining temporal fiducial points associated with a systolic portion of at least one cardiac cycle and defining temporal fiducial points associated with a diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations, acquiring, at each of the plurality of electrode vector configurations and about simultaneously with the sensed heart sounds, an intracardiac impedance signal, extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based at least in part on the defined temporal fiducial points associated with the systolic portion of at least one cardiac cycle and the defined temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle, and determining selection data for each of the plurality of electrode vector configurations based on the extracted measurements), and use the acquired selection data relating to each of the plurality of conduction delays to set one conduction delay of the plurality of conduction delays for delivery of cardiac resynchronization therapy to the patient.

0013Another exemplary implantable medical device method may include delivering cardiac resynchronization therapy to a patient at a plurality of paced conduction delays; acquiring selection data relating to each of the plurality of paced conduction delays for at least one cardiac cycle (e.g., wherein acquiring the selection data at each paced conduction delay may include sensing heart sounds defining temporal fiducial points associated with a systolic portion of at least one cardiac cycle and defining temporal fiducial points associated with a diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations, acquiring, at each of the plurality of electrode vector configurations and about simultaneously with the sensed heart sounds, an intracardiac impedance signal, extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based at least in part on the defined temporal fiducial points associated with the systolic portion of at least one cardiac cycle and the defined temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle, and determining selection data for each of the plurality of electrode vector configurations based on the intracardiac impedance measurements); and using the acquired selection data relating to each of the plurality of conduction delays to set one conduction delay of the plurality of conduction delays for delivery of cardiac resynchronization therapy to the patient.

0014Further, one or more embodiments of the devices or methods may include one or more of the following: the control module may be configured to acquire temporal fiducial points associated with the systolic portion or a defined segment within the systolic portion of at least one cardiac cycle and temporal fiducial points associated with the diastolic portion or a defined segment within the diastolic portion of the at least one cardiac cycle for each of a plurality of electrode vector configurations, the temporal fiducial points associated with the systolic portion of at least one cardiac cycle and the temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle may include at least heart sounds representative of mitral valve closure (MVC) and aortic valve closure (AVC); the temporal fiducial points associated with the systolic portion of at least one cardiac cycle and the temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle may include temporal fiducial points defined by at least intra-cardiac impedance signal minimum and maximum points (e.g., wherein acquiring selection data may include extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based at least in part on the temporal fiducial points defined by the intra-cardiac impedance signal minimum point and maximum point), the temporal fiducial points associated with the systolic portion of at least one cardiac cycle may include at least points associated with a first predetermined portion of an R-R interval and the temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle comprise at least points associated with a second predetermined portion of the R-R interval (e.g., wherein acquiring selection data may include extracting measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based at least in part on temporal fiducial points associated with a first predetermined portion of an R-R interval and based at least in part on temporal fiducial points associated with a second predetermined portion of an R-R interval), acquiring selection data relating to each of the plurality of options of the device parameter for at least one cardiac cycle may include acquiring selection data relating to each of the plurality of options of the device parameter for at least a plurality of cardiac cycles occurring at the end of a respiratory cycle, and extracting measurements from the intracardiac impedance signal may include extracting one or more parameters comprising minimums, maximums, slopes, integrals, differentials, and timing at which one or more of such parameters occurs relative to one or more fiducial points, the control module (e.g., to use the acquired selection data relating to each of the plurality of options of the device parameter to set one option of the plurality of options for delivery of cardiac resynchronization therapy to the patient) may be configured to provide a score for each of the plurality of options of the device parameter based on the acquired selection data for each vector configuration at each of the plurality of paced conduction delays and select an option of plurality of options of the device parameter based on the scores for the plurality of options of the device parameter for delivery of cardiac resynchronization therapy to the patient (e.g., a score may be provided for each of the plurality of options of the device parameter based on the acquired selection data for each vector configuration by giving one or more selection data parameters determined based on the intracardiac impedance measurements different weight in determining a score than other selection data parameters); the control module may be configured to use the acquired selection data to select an electrode vector configuration for delivery of cardiac resynchronization therapy to the patient; extracting measurements from the intracardiac impedance signal may include at least extracting a first derivative of the impedance and/or the timing of minimum impedance relative to a fiducial point; and the control module may be further configured to allow a user to set a window of allowed pacing conduction delays to which the conduction delay may be set. The above summary is not intended to describe each embodiment or every implementation of the present disclosure. A more complete understanding will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

0015<figref idref="DRAWINGS">FIG. 1</figref> is a diagram of an exemplary system including an exemplary implantable medical device (IMD).

0016<figref idref="DRAWINGS">FIG. 2A</figref> is a diagram of the exemplary IMD of <figref idref="DRAWINGS">FIG. 1</figref>.

0017<figref idref="DRAWINGS">FIG. 2B</figref> is a diagram of an enlarged view of a distal end of the electrical lead disposed in the left ventricle of <figref idref="DRAWINGS">FIG. 2A</figref>.

0018<figref idref="DRAWINGS">FIG. 3A</figref> is a block diagram of an exemplary IMD, e.g., the IMD of <figref idref="DRAWINGS">FIGS. 1-2</figref>.

0019<figref idref="DRAWINGS">FIG. 3B</figref> is another block diagram of an exemplary IMD (e.g., an implantable pulse generator) circuitry and associated leads employable in a system such as shown in <figref idref="DRAWINGS">FIGS. 1-2</figref> for providing multiple sensing channels and corresponding pacing channels.

0020<figref idref="DRAWINGS">FIG. 4</figref> is a flow chart of an exemplary method for use in optimizing a device parameter for delivering therapy to a patient's heart, e.g., using the IMD of <figref idref="DRAWINGS">FIGS. 1-3</figref>.

0021<figref idref="DRAWINGS">FIG. 5</figref> is a flow chart of an exemplary method for use acquiring selection data as shown generally, for example, in the method of <figref idref="DRAWINGS">FIG. 4</figref>.

0022<figref idref="DRAWINGS">FIG. 6</figref> is an exemplary graphical depiction of impedance waveforms over a plurality of cardiac cycles superimposed on respiratory cycles for use in describing one or more exemplary methods such as shown, for example, in <figref idref="DRAWINGS">FIG. 5</figref>.

0023<figref idref="DRAWINGS">FIG. 7</figref> is a flow chart of an exemplary method for use acquiring selection data for optimizing AV delay as shown generally, for example, in the method of <figref idref="DRAWINGS">FIG. 4</figref>.

0024<figref idref="DRAWINGS">FIG. 8</figref> is a flow diagram of an exemplary embodiment of a portion of the method of <figref idref="DRAWINGS">FIG. 7</figref> including acquisition of temporal fiducial points.

0025<figref idref="DRAWINGS">FIG. 9</figref> is an exemplary graphical depiction of cardiac cycle events for use in describing one or more exemplary methods such as shown, for example, in <figref idref="DRAWINGS">FIG. 8</figref>.

0026<figref idref="DRAWINGS">FIG. 10</figref> is another flow diagram of an exemplary embodiment of a portion of the method of <figref idref="DRAWINGS">FIG. 7</figref> including acquisition of temporal fiducial points.

0027<figref idref="DRAWINGS">FIG. 11</figref> is an exemplary graphical depiction of impedance waveform morphology associated with ejection and filling for use in describing one or more exemplary methods such as shown, for example, in <figref idref="DRAWINGS">FIG. 10</figref>.

0028<figref idref="DRAWINGS">FIG. 12</figref> is another flow diagram of an exemplary embodiment of a portion of the method of <figref idref="DRAWINGS">FIG. 7</figref> including acquisition of temporal fiducial points.

0029<figref idref="DRAWINGS">FIG. 13</figref> is an exemplary graphical illustration relating R-R intervals to ejection and filling for use in describing one or more exemplary methods such as shown, for example, in <figref idref="DRAWINGS">FIG. 12</figref>.

0030<figref idref="DRAWINGS">FIG. 14</figref> is an exemplary graphical depiction of impedance waveforms over a cardiac cycle for use in describing one or more exemplary methods of acquiring selection data, such as shown, for example, in <figref idref="DRAWINGS">FIG. 5</figref>.

0031<figref idref="DRAWINGS">FIGS. 15-22</figref> are flow charts of a more detailed exemplary method for optimizing AV delay as shown generally, for example, in the method of <figref idref="DRAWINGS">FIG. 5</figref>, including an exemplary scoring process.

0032<figref idref="DRAWINGS">FIGS. 23A-23C and 24</figref> are tables for use in describing a scoring process for optimizing AV delay.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

0033In the following detailed description of illustrative embodiments, reference is made to the accompanying figures of the drawing which form a part hereof, and in which are shown, by way of illustration, specific embodiments which may be practiced. It is to be understood that other embodiments may be utilized and structural changes may be made without departing from (e.g., still falling within) the scope of the disclosure presented hereby.

0034Exemplary methods, devices, and systems shall be described with reference to <figref idref="DRAWINGS">FIGS. 1-24</figref>. It will be apparent to one skilled in the art that elements or processes from one embodiment may be used in combination with elements or processes of the other embodiments, and that the possible embodiments of such methods, devices, and systems using combinations of features set forth herein is not limited to the specific embodiments shown in the Figures and/or described herein. Further, it will be recognized that the embodiments described herein may include many elements that are not necessarily shown to scale. Still further, it will be recognized that timing of the processes and the size and shape of various elements herein may be modified but still fall within the scope of the present disclosure, although certain timings, one or more shapes and/or sizes, or types of elements, may be advantageous over others.

0035As described herein, various exemplary systems, apparatus, and methods may utilize electrodes configured to deliver therapy to tissue of a patient and/or sense one or more signals from the tissue of the patient (e.g., intracardiac impedance, etc.). For example, electrodes may be included as part of an implantable medical device (IMD) and located on one or more leads configured to be located proximate one or more portions of a patient's heart.

0036The exemplary methods and processes described herein may be utilized and implemented by one or more (e.g., two or more, a plurality, etc.) systems, apparatus, and devices that include and/or are coupled to at least one electrode. For example, the exemplary methods and processes may be used by an exemplary therapy system <b>10</b> described herein with reference to <figref idref="DRAWINGS">FIGS. 1-3</figref>. Although a therapy system <b>10</b> is described and depicted herein, it is to be understood that the exemplary methods and processes may be used by any system including computing apparatus capable of analyzing signals from one or more electrodes. The computing apparatus, for example, may be located in an external computer or programmer, may be located in an IMD, or may be located on a server attached to a network.

0037<figref idref="DRAWINGS">FIG. 1</figref> is a conceptual diagram illustrating an exemplary therapy system <b>10</b> that may be used to deliver pacing therapy to a patient <b>14</b>. Patient <b>14</b> may, but not necessarily, be a human. The therapy system <b>10</b> may include an implantable medical device <b>16</b> (IMD), which may be coupled to leads <b>18</b>, <b>20</b>, <b>22</b> and/or a programmer <b>24</b>. The IMD <b>16</b> may be, e.g., an implantable pacemaker, cardioverter, and/or defibrillator, that provides electrical signals to the heart <b>12</b> of the patient <b>14</b> via electrodes coupled to one or more of the leads <b>18</b>, <b>20</b>, <b>22</b>.

0038The leads <b>18</b>, <b>20</b>, <b>22</b> extend into the heart <b>12</b> of the patient <b>14</b> to sense electrical activity of the heart <b>12</b> and/or to deliver electrical stimulation to the heart <b>12</b>. In the example shown in <figref idref="DRAWINGS">FIG. 1</figref>, the right ventricular (RV) lead <b>18</b> extends through one or more veins (not shown), the superior vena cava (not shown), and the right atrium <b>26</b>, and into the right ventricle <b>28</b>. The left ventricular (LV) coronary sinus lead <b>20</b> extends through one or more veins, the vena cava, the right atrium <b>26</b>, and into the coronary sinus <b>30</b> to a region adjacent to the free wall of the left ventricle <b>32</b> of the heart <b>12</b>. The right atrial (RA) lead <b>22</b> extends through one or more veins and the vena cava, and into the right atrium <b>26</b> of the heart <b>12</b>.

0039The IMD <b>16</b> may sense, among other things, electrical signals attendant to the depolarization and repolarization of the heart <b>12</b> via electrodes coupled to at least one of the leads <b>18</b>, <b>20</b>, <b>22</b>. The IMD <b>16</b> may be configured to optimize one or more device parameters (e.g., paced AV delay, paced VV delay, etc.) using, for example, impedance signals sensed at electrodes of the systems (e.g., electrodes located on the leads <b>18</b>, <b>20</b>, <b>22</b>) using the exemplary methods and processes described herein. In some examples, the IMD <b>16</b> provides pacing therapy (e.g., pacing pulses, CRT, etc.) to the heart <b>12</b> based on the electrical signals sensed within the heart <b>12</b>. The IMD <b>16</b> may be operable to adjust one or more device parameters associated with the pacing therapy such as, e.g., paced AV delay and other various timings, pulse wide, amplitude, voltage, burst length, etc. Further, the IMD <b>16</b> may be operable to use various electrode configurations to deliver pacing therapy, which may be unipolar, bipolar, quadripoloar, or further multipolar. For example, a multipolar lead may include several electrodes which can be used for delivering pacing therapy. Hence, a multipolar lead system may provide, or offer, multiple electrical vectors to pace from. A pacing vector may include at least one cathode, which may be at least one electrode located on at least one lead, and at least one anode, which may be at least one electrode located on at least one lead (e.g., the same lead, or a different lead) and/or on the casing, or can, of the IMD. While improvement in cardiac function as a result of the pacing therapy may primarily depend on the cathode, the electrical parameters like impedance, pacing threshold voltage, current drain, longevity, etc. may be more dependent on the pacing vector, which includes both the cathode and the anode. The IMD <b>16</b> may also provide defibrillation therapy and/or cardioversion therapy via electrodes located on at least one of the leads <b>18</b>, <b>20</b>, <b>22</b>. Further, the IMD <b>16</b> may detect arrhythmia of the heart <b>12</b>, such as fibrillation of the ventricles <b>28</b>, <b>32</b>, and deliver defibrillation therapy to the heart <b>12</b> in the form of electrical pulses. In some examples, IMD <b>16</b> may be programmed to deliver a progression of therapies, e.g., pulses with increasing energy levels, until a fibrillation of heart <b>12</b> is stopped.

0040In some examples, a programmer <b>24</b>, which may be a handheld computing device or a computer workstation, may be used by a user, such as a physician, technician, another clinician, and/or patient, to communicate with the IMD <b>16</b> (e.g., to program the IMD <b>16</b>). For example, the user may interact with the programmer <b>24</b> to retrieve information concerning cardiac improvement information, longevity information (e.g., capture threshold information, impedance values, etc.) with respect to one or more electrical vectors, and/or provide sensed data (e.g., heart sound data, impedance signals, etc.). Additionally, the user may interact with the programmer <b>24</b> to select one or more optimal device parameters, e.g., for use in delivering therapy, such as AV delay and VV delay, electrode vector to be used for pacing, etc. Further, the user may interact with the programmer <b>24</b> to retrieve information concerning selection data associated with the IMD <b>16</b> and/or the pacing therapy delivered therewith. For instance, computing apparatus located in one or both of the IMD <b>16</b> and the programmer <b>24</b> may be configured to analyze or evaluate signals (e.g., impedance signals, heart sounds, R-R interval, etc. or data associated therewith) to identify one or more optimal device parameters (e.g., AV delay). The IMD <b>16</b> and the programmer <b>24</b> may communicate via wireless communication using any techniques known in the art. Examples of communication techniques may include, e.g., low frequency or radiofrequency (RF) telemetry, but other techniques are also contemplated. The IMD and programmer may be used to initialize the IMD with optimized device parameters as described herein or the IMD may carry out such optimization without the programmer (e.g., optimization may be provided at implant or after implant).

0041<figref idref="DRAWINGS">FIG. 2A</figref> is a conceptual diagram illustrating the IMD <b>16</b> and the leads <b>18</b>, <b>20</b>, <b>22</b> of therapy system <b>10</b> of <figref idref="DRAWINGS">FIG. 1</figref> in more detail. The leads <b>18</b>, <b>20</b>, <b>22</b> may be electrically coupled to a therapy delivery module (e.g., for delivery of pacing therapy), a sensing module (e.g., for sensing one or more signals from one or more electrodes), and/or any other modules of the IMD <b>16</b> via a connector block <b>34</b>. In some examples, the proximal ends of the leads <b>18</b>, <b>20</b>, <b>22</b> may include electrical contacts that electrically couple to respective electrical contacts within the connector block <b>34</b> of the IMD <b>16</b>. In addition, in some examples, the leads <b>18</b>, <b>20</b>, <b>22</b> may be mechanically coupled to the connector block <b>34</b> with the aid of set screws, connection pins, or another suitable mechanical coupling mechanism.

0042Each of the leads <b>18</b>, <b>20</b>, <b>22</b> includes an elongated insulative lead body, which may carry a number of conductors (e.g., concentric coiled conductors, straight conductors, etc.) separated from one another by insulation (e.g., tubular insulative sheaths). In the illustrated example, bipolar electrodes <b>40</b>, <b>42</b> are located proximate to a distal end of the lead <b>18</b>. In addition, the bipolar electrodes <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b> are located proximate to a distal end of the lead <b>20</b> and the bipolar electrodes <b>48</b>, <b>50</b> are located proximate to a distal end of the lead <b>22</b>.

0043The electrodes <b>40</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b> may take the form of ring electrodes mounted with respect to, and the electrodes <b>42</b>, <b>50</b> may take the form of extendable helix tip electrodes mounted retractably within, the insulative electrode heads <b>52</b>, <b>54</b>, <b>56</b>. Each of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b> may be electrically coupled to a respective one of the conductors (e.g., coiled and/or straight) within the lead body of its associated lead <b>18</b>, <b>20</b>, <b>22</b>, and thereby coupled to respective ones of the electrical contacts on the proximal end of the leads <b>18</b>, <b>20</b>, <b>22</b>.

0044Additionally, electrodes <b>44</b>, <b>45</b>, <b>46</b> and <b>47</b> may have an electrode surface area of about 5.3 mm²to about 5.8 mm². Electrodes <b>44</b>, <b>45</b>, <b>46</b>, and <b>47</b> may also be referred to as LV<b>1</b>, LV<b>2</b>, LV<b>3</b>, and LV<b>4</b>, respectively. The LV electrodes (i.e., left ventricle electrode <b>1</b> (LV<b>1</b>) <b>44</b>, left ventricle electrode <b>2</b> (LV<b>2</b>) <b>45</b>, left ventricle electrode <b>3</b> (LV<b>3</b>) <b>46</b>, and left ventricle <b>4</b> (LV<b>4</b>) <b>47</b> etc.) on the lead <b>20</b> can be spaced apart at variable distances. For example, electrode <b>44</b> may be a distance of, e.g., about 21 millimeters (mm), away from electrode <b>45</b>, electrodes <b>45</b> and <b>46</b> may be spaced a distance of, e.g. about 1.3 mm to about 1.5 mm, away from each other, and electrodes <b>46</b> and <b>47</b> may be spaced a distance of, e.g. 20 mm to about 21 mm, away from each other.

0045The electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b> may further be used to sense electrical signals (e.g., morphological waveforms within electrograms (EGM), etc.) attendant to the depolarization and repolarization of the heart <b>12</b>, sense intracardiac impedance, etc. The sensed electrical signals may be used to determine which of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b> are the most effective in improving cardiac function, may be used to optimize device parameters, acquire selection data as described herein, etc. The electrical signals are conducted to the IMD <b>16</b> via the respective leads <b>18</b>, <b>20</b>, <b>22</b>. In some examples, the IMD <b>16</b> may also deliver pacing pulses via the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b> to cause depolarization of cardiac tissue of the patient's heart <b>12</b>. In some examples, as illustrated in <figref idref="DRAWINGS">FIG. 2A</figref>, the IMD <b>16</b> includes one or more housing electrodes, such as housing electrode <b>58</b>, which may be formed integrally with an outer surface of a housing <b>60</b> (e.g., hermetically-sealed housing) of the IMD <b>16</b> or otherwise coupled to the housing <b>60</b>. Any of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b> and <b>50</b> may be used for unipolar sensing or pacing in combination with housing electrode <b>58</b>. In other words, any of electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b> may be used in combination to form a sensing vector (e.g., a sensing vector that may be used to evaluate and/or analyze the pacing therapy, used to acquire selection data, acquire intracardiac impedance signal, etc.). It is generally understood by those skilled in the art that other electrodes can also be selected to define, or be used for, pacing and sensing vectors. Further, any of electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, which are not being used to deliver pacing therapy, may be used to sense electrical activity during pacing therapy.

0046As described in further detail with reference to <figref idref="DRAWINGS">FIGS. 3A-3B</figref>, the housing <b>60</b> may enclose a therapy delivery module that may include a stimulation generator for generating cardiac pacing pulses and defibrillation or cardioversion shocks, as well as a sensing module for monitoring the patient's heart rhythm. The leads <b>18</b>, <b>20</b>, <b>22</b> may also include elongated electrodes <b>62</b>, <b>64</b>, <b>66</b>, respectively, which may take the form of a coil. The IMD <b>16</b> may deliver defibrillation shocks to the heart <b>12</b> via any combination of the elongated electrodes <b>62</b>, <b>64</b>, <b>66</b> and the housing electrode <b>58</b>. The electrodes <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b> may also be used to deliver cardioversion pulses to the heart <b>12</b>. Further, the electrodes <b>62</b>, <b>64</b>, <b>66</b> may be fabricated from any suitable electrically conductive material, such as, but not limited to, platinum, platinum alloy, and/or other materials known to be usable in implantable defibrillation electrodes. Since electrodes <b>62</b>, <b>64</b>, <b>66</b> are not generally configured to deliver pacing therapy, any of electrodes <b>62</b>, <b>64</b>, <b>66</b> may be used to sense electrical activity (e.g., for use in acquiring intracardiac impedance waveforms, for acquiring signals for use in providing impedance measurements, for use in analyzing pacing therapy effectiveness, etc.) and may be used in combination with any of electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>. In at least one embodiment, the RV elongated electrode <b>62</b> may be used to sense electrical activity of a patient's heart during the delivery of pacing therapy (e.g., in combination with the housing electrode <b>58</b> forming a RV elongated coil, or defibrillation electrode-to-housing electrode vector).

0047The configuration of the exemplary therapy system <b>10</b> illustrated in <figref idref="DRAWINGS">FIGS. 1-2</figref> is merely one example. In other examples, the therapy system may include epicardial leads and/or patch electrodes instead of or in addition to the transvenous leads <b>18</b>, <b>20</b>, <b>22</b> illustrated in <figref idref="DRAWINGS">FIG. 1</figref>. Further, in one or more embodiments, the IMD <b>16</b> need not be implanted within the patient <b>14</b>. For example, the IMD <b>16</b> may deliver various cardiac therapies to the heart <b>12</b> via percutaneous leads that extend through the skin of the patient <b>14</b> to a variety of positions within or outside of the heart <b>12</b>. In one or more embodiments, the system <b>10</b> may utilize wireless pacing (e.g., using energy transmission to the intracardiac pacing component(s) via ultrasound, inductive coupling, RF, etc.) and sensing cardiac activation using electrodes on the can/housing and/or on subcutaneous leads.

0048In other examples of therapy systems that provide electrical stimulation therapy to the heart <b>12</b>, such therapy systems may include any suitable number of leads coupled to the IMD <b>16</b>, and each of the leads may extend to any location within or proximate to the heart <b>12</b>. For example, other examples of therapy systems may include three transvenous leads located as illustrated in <figref idref="DRAWINGS">FIGS. 1-2</figref>. Still further, other therapy systems may include a single lead that extends from the IMD <b>16</b> into the right atrium <b>26</b> or the right ventricle <b>28</b>, or two leads that extend into a respective one of the right atrium <b>26</b> and the right ventricle <b>28</b>.

0049<figref idref="DRAWINGS">FIG. 3A</figref> is a functional block diagram of one exemplary configuration of the IMD <b>16</b>. As shown, the IMD <b>16</b> may include a control module <b>81</b>, a therapy delivery module <b>84</b> (e.g., which may include a stimulation generator), a sensing module <b>86</b>, and a power source <b>90</b>.

0050The control module <b>81</b> may include a processor <b>80</b>, memory <b>82</b>, and a telemetry module <b>88</b>. The memory <b>82</b> may include computer-readable instructions that, when executed, e.g., by the processor <b>80</b>, cause the IMD <b>16</b> and/or the control module <b>81</b> to perform various functions attributed to the IMD <b>16</b> and/or the control module <b>81</b> described herein (e.g., including capture management). Further, the memory <b>82</b> may include any volatile, non-volatile, magnetic, optical, and/or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, and/or any other digital media. An exemplary capture management module may be the left ventricular capture management (LVCM) module described in U.S. Pat. No. 7,684,863 entitled “LV THRESHOLD MEASUREMENT AND CAPTURE MANAGEMENT” and issued Mar. 23, 2010, which is incorporated herein by reference in its entirety.

0051The processor <b>80</b> of the control module <b>81</b> may include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), and/or equivalent discrete or integrated logic circuitry. In some examples, the processor <b>80</b> may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, and/or one or more FPGAs, as well as other discrete or integrated logic circuitry. The functions attributed to the processor <b>80</b> herein may be embodied as software, firmware, hardware, or any combination thereof.

0052The control module <b>81</b> may be used to determine device parameters (e.g., paced AV delay, paced VV delay, an effective electrode vector configuration, etc.) using the exemplary methods and/or processes described herein according to a selected one or more programs, which may be stored in the memory <b>82</b>. Further, the control module <b>81</b> may control the therapy delivery module <b>84</b> to deliver therapy (e.g., electrical stimulation therapy such as pacing) to the heart <b>12</b> according to a selected one or more therapy programs, which may be stored in the memory <b>82</b>. More specifically, the control module <b>81</b> (e.g., the processor <b>80</b>) may control various parameters of the electrical stimulus delivered by the therapy delivery module <b>84</b> such as, e.g., AV delays, VV delays, pacing pulses with the amplitudes, pulse widths, frequency, or electrode polarities, etc., which may be specified by one or more selected therapy programs (e.g., AV delay selection and/or adjustment programs as described herein, VV delay selection and/or adjustment programs as described herein, pacing therapy programs, pacing recovery programs, capture management programs, etc.). As shown, the therapy delivery module <b>84</b> is electrically coupled to electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b>, e.g., via conductors of the respective lead <b>18</b>, <b>20</b>, <b>22</b>, or, in the case of housing electrode <b>58</b>, via an electrical conductor disposed within housing <b>60</b> of IMD <b>16</b>. Therapy delivery module <b>84</b> may be configured to generate and deliver electrical stimulation therapy such as pacing therapy to the heart <b>12</b> using one or more of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b>.

0053For example, therapy delivery module <b>84</b> may deliver pacing stimulus (e.g., pacing pulses) via ring electrodes <b>40</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b> coupled to leads <b>18</b>, <b>20</b>, and <b>22</b>, respectively, and/or helical tip electrodes <b>42</b> and <b>50</b> of leads <b>18</b> and <b>22</b>. Further, for example, therapy delivery module <b>84</b> may deliver defibrillation shocks to heart <b>12</b> via at least two of electrodes <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b>. In some examples, therapy delivery module <b>84</b> may be configured to deliver pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, therapy delivery module <b>84</b> may be configured to deliver one or more of these types of stimulation in the form of other signals, such as sine waves, square waves, and/or other substantially continuous time signals.

0054The IMD <b>16</b> may further include a switch module <b>85</b> and the control module <b>81</b> (e.g., the processor <b>80</b>) may use the switch module <b>85</b> to select, e.g., via a data/address bus, which of the available electrodes are used to deliver therapy such as pacing pulses for pacing therapy, or which of the available electrodes are used for sensing (e.g., select electrode vector configurations for pacing, select electrode vector configurations for sensing, etc.). The switch module <b>85</b> may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable to selectively couple the sensing module <b>86</b> and/or the therapy delivery module <b>84</b> to one or more selected electrodes. More specifically, the therapy delivery module <b>84</b> may include a plurality of pacing output circuits. Each pacing output circuit of the plurality of pacing output circuits may be selectively coupled, e.g., using the switch module <b>85</b>, to one or more of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b> (e.g., a pair of electrodes for delivery of therapy to a pacing vector). In other words, each electrode can be selectively coupled to one of the pacing output circuits of the therapy delivery module using the switching module <b>85</b>.

0055The sensing module <b>86</b> is coupled (e.g., electrically coupled) to sensing apparatus, which may include, among additional sensing apparatus, the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b> to monitor electrical activity of the heart <b>12</b>, e.g., electrocardiogram (ECG)/electrogram (EGM) signals, etc. The ECG/EGM signals may be used to provide information for one or more functions, including those described herein for setting one or more device parameters (e.g., intializing and/or adjusting device parameters to provide optimization thereof, such as AV delay and VV delay, for example, by monitoring or measuring the signals for analysis by the control module <b>81</b>, the programmer <b>24</b>, etc.). Further, the ECG/EGM signals may be used to measure or monitor activation times (e.g., ventricular activations times, etc.), heart rate (HR), heart rate variability (HRV), heart rate turbulence (HRT), deceleration/acceleration capacity, deceleration sequence incidence, T-wave alternans (TWA), P-wave to P-wave intervals (also referred to as the P-P intervals or A-A intervals), R-wave to R-wave intervals (also referred to as the R-R intervals or V-V intervals), P-wave to QRS complex intervals (also referred to as the P-R intervals, A-V intervals, or P-Q intervals), QRS-complex morphology, ST segment (i.e., the segment that connects the QRS complex and the T-wave), T-wave changes, QT intervals, electrical vectors, etc.

0056The switch module <b>85</b> may be also be used with the sensing module <b>86</b> to select which of the available electrodes are used, or enabled, to, e.g., sense electrical activity of the patient's heart (e.g., one or more electrical vector configurations using any combination of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b>). Likewise, the switch module <b>85</b> may also be used with the sensing module <b>86</b> to select which of the available electrodes are not to be used (e.g., disabled) to, e.g., sense electrical activity of the patient's heart (e.g., one or more electrical vector configurations using any combination of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b>), etc. In some examples, the control module <b>81</b> may select the electrodes that function as sensing electrodes via the switch module within the sensing module <b>86</b>, e.g., by providing signals via a data/address bus.

0057In some examples, sensing module <b>86</b> includes a channel that includes an amplifier with a relatively wider pass band than the R-wave or P-wave amplifiers. Signals from the selected sensing electrodes may be provided to a multiplexer, and thereafter converted to multi-bit digital signals by an analog-to-digital converter for storage in memory <b>82</b>, e.g., as an electrogram (EGM). In some examples, the storage of such EGMs in memory <b>82</b> may be under the control of a direct memory access circuit. The control module <b>81</b> (e.g., using the processor <b>80</b>) may employ digital signal analysis techniques to characterize the digitized signals stored in memory <b>82</b> to analyze and/or classify one or more morphological waveforms of the EGM signals to determine pacing therapy effectiveness, etc. For example, the processor <b>80</b> may be configured to determine, or obtain, one or more features of one or more sensed morphological waveforms within one or more electrical vectors of the patient's heart and store the one or more features within the memory <b>82</b> for use in comparing features, values, etc. of the waveforms to set device parameters, etc.

0058In some examples, the control module <b>81</b> may operate as an interrupt driven device, and may be responsive to interrupts from pacer timing and control module, where the interrupts may correspond to the occurrences of sensed P-waves and R-waves and the generation of cardiac pacing pulses. Any necessary mathematical calculations may be performed by the processor <b>80</b> and any updating of the values or intervals controlled by the pacer timing and control module may take place following such interrupts. A portion of memory <b>82</b> may be configured as a plurality of recirculating buffers, capable of holding one or more series of measured intervals, which may be analyzed by, e.g., the processor <b>80</b> in response to the occurrence of a pace or sense interrupt to determine whether the patient's heart <b>12</b> is presently exhibiting atrial or ventricular tachyarrhythmia.

0059In one or more embodiments, one or more electrical vector configurations, for example, using any combination of the electrodes <b>40</b>, <b>42</b>, <b>44</b>, <b>45</b>, <b>46</b>, <b>47</b>, <b>48</b>, <b>50</b>, <b>58</b>, <b>62</b>, <b>64</b>, <b>66</b> and/or any other electrodes may further be used to sense impedance (e.g., intracardiac impedance signals within the patient's heart <b>12</b>). Impedance signals can be measured in a tissue segment (e.g., heart tissue segment) located in an electrode vector field between any two or more of the electrodes by measuring a voltage between two or more selected electrodes upon injecting a current between two or more selected electrodes; the impedance being determined, for example, based on the injected current and the measured voltage. The impedance may change due to a change in the characteristics of the tissue in the electrode vector field (e.g., degradation of the cellular wall due to disease), due to a change in the distance between electrodes (e.g., the change in distance between the left ventricle and the right ventricle), and/or due to a change in blood volume contained with the electrode vector field.

0060For example, the IMD <b>16</b> may measure an intracardiac impedance signal by injecting a current and measuring a voltage between electrodes of an electrode vector configuration (e.g., selected electrodes). For example, the IMD <b>16</b> may measure an impedance signal by injecting a current (e.g., a non-pacing threshold current) between electrode <b>42</b> and an electrode (not depicted) located in the right ventricle proximate the tricuspid valve and measuring a voltage between electrode <b>40</b> and the electrode (not depicted) located in the right ventricle proximate the tricuspid valve. Still further, for example, the IMD <b>16</b> may measure an impedance signal by injecting a current between electrode <b>50</b> and electrode <b>42</b> and measuring a voltage between electrode <b>48</b> and electrode <b>40</b>. One will recognize that other vector pair configurations may be used for stimulation and measurement. Impedance can be measured between any set of electrodes that encompass the tissue or cardiac chamber of interest. Thus, one can inject current and measure voltage to calculate the impedance on the same two electrodes (a bipolar configuration) or inject current and measure voltage on two separate pairs of electrodes (e.g., one pair for current injection and one pair for voltage sense), hence, a quadrapolar configuration. For a quadrapolar electrode configuration, the current injection and voltage sense electrodes should be in line with each other (or closely parallel to) and the voltage sense electrodes should be within the current sense field. For example, if one injected current between the SVC coil electrode and the RV tip electrode, voltage sense may be between the RVC coil electrode and RV ring electrode. The impedance vectors can be configured to encompass a particular anatomical area of interest, such as the atrium or ventricles.

0061The exemplary methods and/or devices described herein may monitor one or more electrode vector configurations. Further, multiple impedance vectors may be measured concurrently and/or periodically relative to another. In at least one embodiment, the exemplary methods and/or devices may use impedance waveforms to acquire selection data (e.g., to find applicable fiducial points, to allow extraction of measurements from such waveforms, etc.) for optimizing CRT.

0062As used herein, the term “impedance signal” is not limited to a raw impedance signal. It should be implied that raw impedance signals may be processed, normalized, and/or filtered (e.g., to remove artifacts, noise, static, EMI, and/or extraneous signals) to provide the impedance signal. Further, the term “impedance signal” may include various mathematical derivatives thereof including real and imaginary portions of the impedance signal, a conductance signal based on the impedance (i.e., the reciprocal or inverse of impedance), etc. In other words, the term “impedance signal” may be understood to include conductance signals, i.e. signals that are the reciprocal of the impedance signal.

0063Further, other sensor apparatus <b>93</b> may be coupled to sensing module <b>86</b> via any suitable interface (e.g., electrically coupled, coupled via amplifiers, analog to digital convertors, buffers, etc.) to monitor other heart related activity, such as acoustic data (e.g., heart sounds, including mitral valve closure and aortic valve closure, S<b>1</b> and S<b>2</b> as described herein, etc.). For example, in one or more embodiments, such sensor apparatus <b>93</b> may include any suitable transducer components (e.g., mounted within the implanted device, mounted on the can of the device, etc.) for sensing valve activity, such as a sonomicrometer, an accelerometer, a cardiomechanical sensor (CMES) employing embedded piezoelectric material on an implanted lead or alternate piezoelectric sensor. In other embodiments, heart valve events, such as mitral valve closure and aortic valve closure, may be detected using non-acoustic sensors, including, for example, sensors embedded in the myocardium or pressure Sensors implanted to detect chamber pressures, etc. Such detected valve events (e.g., heart sounds) may be used to provide information for one or more functions, including those described herein for setting one or more device parameters (e.g., intializing or adjusting device parameters to provide optimization thereof, such as AV delay and VV delay, for example, by monitoring or measuring the signals for analysis by the control module <b>81</b>, the programmer <b>24</b>, etc.).

0064The telemetry module <b>88</b> of the control module <b>81</b> may include any suitable hardware, firmware, software, or any combination thereof for communicating with another device, such as the programmer <b>24</b> as described herein with respect to <figref idref="DRAWINGS">FIG. 1</figref>. For example, under the control of the processor <b>80</b>, the telemetry module <b>88</b> may receive downlink telemetry from and send uplink telemetry to the programmer <b>24</b> with the aid of an antenna, which may be internal and/or external. The processor <b>80</b> may provide the data to be uplinked to the programmer <b>24</b> and the control signals for the telemetry circuit within the telemetry module <b>88</b>, e.g., via an address/data bus. In some examples, the telemetry module <b>88</b> may provide received data to the processor <b>80</b> via a multiplexer.

0065In at least one embodiment, the control module <b>81</b> may transmit impedance signal data (e.g., produced by using various electrodes proximate the patient's heart <b>12</b>) and/or any other data usable for setting device parameters as described herein using the telemetry module <b>88</b> to an external device, such as the programmer <b>24</b>, such that a clinician and/or patient may use such data to optimize CRT. In other words, the IMD <b>16</b> may transmit data based on the impedance signal data to an external device such that a clinician may use the data for diagnostic purposes, followup visit adjustment, therapy adjustment (e.g., CRT adjustment), etc. For example, a clinician may use transmitted data to optimize CRT provided by the IMD <b>16</b> (e.g., modifying or adjusting the AV and/or VV delays).

0066The various components of the IMD <b>16</b> are further coupled to a power source <b>90</b>, which may include a rechargeable or non-rechargeable battery. A non-rechargeable battery may be selected to last for several years, while a rechargeable battery may be inductively charged from an external device, e.g., on a daily or weekly basis.

0067<figref idref="DRAWINGS">FIG. 3B</figref> is another embodiment of a functional block diagram for IMD <b>16</b>. <figref idref="DRAWINGS">FIG. 3B</figref> depicts bipolar RA lead <b>22</b>, bipolar RV lead <b>18</b>, and bipolar LV CS lead <b>20</b> without the LA CS pace/sense electrodes and coupled with an implantable pulse generator (IPG) circuit <b>31</b> having programmable modes and parameters of a bi-ventricular DDD/R type known in the pacing art. In turn, the sensor signal processing circuit <b>91</b> indirectly couples to the timing circuit <b>83</b> and via data and control bus to microcomputer circuitry <b>33</b>. The IPG circuit <b>31</b> is illustrated in a functional block diagram divided generally into a microcomputer circuit <b>33</b> and a pacing circuit <b>21</b>. The pacing circuit <b>21</b> includes the digital controller/timer circuit <b>83</b>, the output amplifiers circuit <b>51</b>, the sense amplifiers circuit <b>55</b>, the RF telemetry transceiver <b>41</b>, the activity sensor circuit <b>35</b> as well as a number of other circuits and components described below.

0068Crystal oscillator circuit <b>89</b> provides the basic timing clock for the pacing circuit <b>21</b>, while battery <b>29</b> provides power. Power-on-reset circuit <b>87</b> responds to initial connection of the circuit to the battery for defining an initial operating condition and similarly, resets the operative state of the device in response to detection of a low battery condition. Reference mode circuit <b>37</b> generates stable voltage reference and currents for the analog circuits within the pacing circuit <b>21</b>, while analog to digital converter ADC and multiplexer circuit <b>39</b> digitizes analog signals and voltage to provide real time telemetry of cardiac signals from sense amplifiers <b>55</b>, for uplink transmission via RF transmitter and receiver circuit <b>41</b>. Voltage reference and bias circuit <b>37</b>, ADC and multiplexer <b>39</b>, power-on-reset circuit <b>87</b> and crystal oscillator circuit <b>89</b> may correspond to any of those presently used in current marketed implantable cardiac pacemakers.

0069If the IPG is programmed to a rate responsive mode, the signals output by one or more physiologic sensor are employed as a rate control parameter (RCP) to derive a physiologic escape interval. For example, the escape interval is adjusted proportionally to the patient's activity level developed in the patient activity sensor (PAS) circuit <b>35</b> in the depicted, exemplary IPG circuit <b>31</b>. The patient activity sensor <b>27</b> is coupled to the IPG housing and may take the form of a piezoelectric crystal transducer as is well known in the art and its output signal is processed and used as the RCP. Sensor <b>27</b> generates electrical signals in response to sensed physical activity that are processed by activity circuit <b>35</b> and provided to digital controller/timer circuit <b>83</b>. Activity circuit <b>35</b> and associated sensor <b>27</b> may correspond to the circuitry disclosed in U.S. Pat. No. 5,052,388 entitled “METHOD AND APPARATUS FOR IMPLEMENTING ACTIVITY SENSING IN A PULSE GENERATOR” issued on Oct. 1, 1991 and U.S. Pat. No. 4,428,378 entitled “RATE ADAPTIVE PACER” issued on Jan. 31, 1984, each of which are incorporated herein by reference in their entireties.

0070Similarly, the exemplary systems, apparatus, and methods described herein may be practiced in conjunction with alternate types of sensors such as oxygenation sensors, pressure sensors, pH sensors and respiration sensors, all well known for use in providing pacing capabilities. For example, at least in one embodiment, respiration may be sensed using measurements of transthoracic impedance (e.g., impedance between an electrode implanted in the heart and an electrode on the housing of the implanted device, such as, for example, by measuring a voltage between electrode <b>40</b> and electrode <b>58</b>); may be sensed using EGM derived respiration (e.g., which may be derived from the change in the amplitude of the far-field EGM, for example, sensed by electrode <b>66</b> and <b>58</b>, due to respiration); respiratory signals may be acquired through the selected electrode vector configuration in an effort to measure: respiratory rate, respiratory tidal volume, inspiratory effort, and expiratory effort; etc.

0071Further, acoustic sensors (not shown) may be used as described herein (e.g., to detect heart sounds), or other sensors (e.g., for detection of valve closures) may be used, with such signals representative thereof being adapted for use by the IPG circuit <b>31</b>. Alternately, QT time may be used as the rate indicating parameter, in which case no extra sensor is required. Similarly, the exemplary embodiments described herein may also be practiced in non-rate responsive pacemakers.

0072Data transmission to and from the external programmer is accomplished by way of the telemetry antenna <b>57</b> and an associated RF transceiver <b>41</b>, which serves both to demodulate received downlink telemetry and to transmit uplink telemetry. Uplink telemetry capabilities will typically include the ability to transmit stored digital information, e.g. operating modes and parameters, EGM histograms, and other events, as well as real time EGMs of atrial and/or ventricular electrical activity and marker channel pulses indicating the occurrence of sensed and paced depolarizations in the atrium and ventricle, as are well known in the pacing art.

0073Microcomputer <b>33</b> contains a microprocessor <b>80</b> and associated system clock and on-processor RAM and ROM chips <b>82</b>A and <b>82</b>B, respectively. In addition, microcomputer circuit <b>33</b> includes a separate RAM/ROM chip <b>82</b>C to provide additional memory capacity. Microprocessor <b>80</b> normally operates in a reduced power consumption mode and is interrupt driven. Microprocessor <b>80</b> is awakened in response to defined interrupt events, which may include A-TRIG, RV-TRIG, LV-TRIG signals generated by timers in digital timer/controller circuit <b>83</b> and A-EVENT, RV-EVENT, and LV-EVENT signals generated by sense amplifiers circuit <b>55</b>, among others. The specific values of the intervals and delays timed out by digital controller/timer circuit <b>83</b> are controlled by the microcomputer circuit <b>33</b> by way of data and control bus from programmed-in parameter values and operating modes. In addition, if programmed to operate as a rate responsive pacemaker, a timed interrupt, e.g., every cycle or every two seconds, may be provided in order to allow the microprocessor to analyze the activity sensor data and update the basic A-A, V-A, or V-V escape interval, as applicable. In addition, the microprocessor <b>80</b> may also serve to define variable, operative AV delay intervals and the energy delivered to each ventricle.

0074In one embodiment, microprocessor <b>80</b> is a custom microprocessor adapted to fetch and execute instructions stored in RAM/ROM unit <b>82</b> in a conventional manner. It is contemplated, however, that other implementations may be suitable to practice the present invention. For example, an off-the-shelf, commercially available microprocessor or microcontroller, or custom application-specific, hardwired logic, or state-machine type circuit may perform the functions of microprocessor <b>80</b>.

0075Digital controller/timer circuit <b>83</b> operates under the general control of the microcomputer <b>33</b> to control timing and other functions within the pacing circuit <b>21</b> and includes a set of timing and associated logic circuits of which certain ones pertinent to the present invention are depicted. The depicted timing circuits include URI/LRI timers <b>83</b>A, V-V delay timer <b>83</b>B, intrinsic interval timers <b>83</b>C for timing elapsed V-EVENT to V-EVENT intervals or V-EVENT to A-EVENT intervals or the V-V conduction interval, escape interval timers <b>83</b>D for timing A-A, V-A, and/or V-V pacing escape intervals, an AV delay interval timer <b>83</b>E for timing the A-LVp delay (or A-RVp delay) from a preceding A-EVENT or A-TRIG, a post-ventricular timer <b>83</b>F for timing post-ventricular time periods, and a date/time clock <b>83</b>G.

0076The AV delay interval timer <b>83</b>E is loaded with an appropriate delay interval for one ventricular chamber (e.g., either an A-RVp delay or an A-LVp delay as determined using known methods) to time-out starting from a preceding A-PACE or A-EVENT. The interval timer <b>83</b>E triggers pacing stimulus delivery, and can be based on one or more prior cardiac cycles (or from a data set empirically derived for a given patient).

0077The post-event timer <b>83</b>F times out the post-ventricular time period following an RV-EVENT or LV-EVENT or a RV-TRIG or LV-TRIG and post-atrial time periods following an A-EVENT or A-TRIG. The durations of the post-event time periods may also be selected as programmable parameters stored in the microcomputer <b>33</b>. The post-ventricular time periods include the PVARP, a post-atrial ventricular blanking period (PAVBP), a ventricular blanking period (VBP), a post-ventricular atrial blanking period (PVARP) and a ventricular refractory period (VRP) although other periods can be suitably defined depending, at least in part, on the operative circuitry employed in the pacing engine. The post-atrial time periods include an atrial refractory period (ARP) during which an A-EVENT is ignored for the purpose of resetting any AV delay, and an atrial blanking period (ABP) during which atrial sensing is disabled. It should be noted that the starting of the post-atrial time periods and the AV delays can be commenced substantially simultaneously with the start or end of each A-EVENT or A-TRIG or, in the latter case, upon the end of the A-PACE which may follow the A-TRIG. Similarly, the starting of the post-ventricular time periods and the V-A escape interval can be commenced substantially simultaneously with the start or end of the V-EVENT or V-TRIG or, in the latter case, upon the end of the V-PACE which may follow the V-TRIG. The microprocessor <b>80</b> also optionally calculates AV delays, post-ventricular time periods, and post-atrial time periods that vary with the sensor based escape interval established in response to the RCP(s) and/or with the intrinsic atrial rate.

0078The output amplifiers circuit <b>51</b> contains a RA pace pulse generator (and a LA pace pulse generator if LA pacing is provided), a RV pace pulse generator, and a LV pace pulse generator or corresponding to any of those presently employed in commercially marketed cardiac pacemakers providing atrial and ventricular pacing. In order to trigger generation of an RV-PACE or LV-PACE pulse, digital controller/timer circuit <b>83</b> generates the RV-TRIG signal at the time-out of the A-RVp delay (in the case of RV pre-excitation) or the LV-TRIG at the time-out of the A-LVp delay (in the case of LV pre-excitation) provided by AV delay interval timer <b>83</b>E (or the V-V delay timer <b>83</b>B). Similarly, digital controller/timer circuit <b>83</b> generates an RA-TRIG signal that triggers output of an RA-PACE pulse (or an LA-TRIG signal that triggers output of an LA-PACE pulse, if provided) at the end of the V-A escape interval timed by escape interval timers <b>83</b>D.

0079The output amplifiers circuit <b>51</b> includes switching circuits for coupling selected pace electrode pairs from among the lead conductors and the IND CAN electrode <b>20</b> to the RA pace pulse generator (and LA pace pulse generator if provided), RV pace pulse generator and LV pace pulse generator. Pace/sense electrode pair selection and control circuit <b>53</b> selects lead conductors and associated pace electrode pairs to be coupled with the atrial and ventricular output amplifiers within output amplifiers circuit <b>51</b> for accomplishing RA, LA, RV and LV pacing.

0080The sense amplifiers circuit <b>55</b> contains sense amplifiers corresponding to any of those presently employed in contemporary cardiac pacemakers for atrial and ventricular pacing and sensing. High impedance P-wave and R-wave sense amplifiers may be used to amplify a voltage difference signal that is generated across the sense electrode pairs by the passage of cardiac depolarization wavefronts. The high impedance sense amplifiers use high gain to amplify the low amplitude signals and rely on pass band filters, time domain filtering and amplitude threshold comparison to discriminate a P-wave or R-wave from background electrical noise. Digital controller/timer circuit <b>83</b> controls sensitivity settings of the atrial and ventricular sense amplifiers <b>55</b>.

0081The sense amplifiers are typically uncoupled from the sense electrodes during the blanking periods before, during, and after delivery of a pace pulse to any of the pace electrodes of the pacing system to avoid saturation of the sense amplifiers. The sense amplifiers circuit <b>55</b> includes blanking circuits for uncoupling the selected pairs of the lead conductors and the IND-CAN electrode <b>20</b> from the inputs of the RA sense amplifier (and LA sense amplifier if provided), RV sense amplifier and LV sense amplifier during the ABP, PVABP and VBP. The sense amplifiers circuit <b>55</b> also includes switching circuits for coupling selected sense electrode lead conductors and the IND-CAN electrode <b>20</b> to the RA sense amplifier (and LA sense amplifier if provided), RV sense amplifier and LV sense amplifier. Again, sense electrode selection and control circuit <b>53</b> selects conductors and associated sense electrode pairs to be coupled with the atrial and ventricular sense amplifiers within the output amplifiers circuit <b>51</b> and sense amplifiers circuit <b>55</b> for accomplishing RA, LA, RV and LV sensing along desired unipolar and bipolar sensing vectors.

0082Right atrial depolarizations or P-waves in the RA-SENSE signal that are sensed by the RA sense amplifier result in a RA-EVENT signal that is communicated to the digital controller/timer circuit <b>83</b>. Similarly, left atrial depolarizations or P-waves in the LA-SENSE signal that are sensed by the LA sense amplifier, if provided, result in a LA-EVENT signal that is communicated to the digital controller/timer circuit <b>83</b>. Ventricular depolarizations or R-waves in the RV-SENSE signal are sensed by a ventricular sense amplifier result in an RV-EVENT signal that is communicated to the digital controller/timer circuit <b>83</b>. Similarly, ventricular depolarizations or R-waves in the LV-SENSE signal are sensed by a ventricular sense amplifier result in an LV-EVENT signal that is communicated to the digital controller/timer circuit <b>83</b>. The RV-EVENT, LV-EVENT, and RA-EVENT, LA-SENSE signals may be refractory or non-refractory, and can inadvertently be triggered by electrical noise signals or aberrantly conducted depolarization waves rather than true R-waves or P-waves.

0083In one or more embodiments of the methods and/or devices described herein, various patient physiological parameters (e.g., intracardiac impedance, heart sounds, cardiac cycle intervals such as R-R interval, etc.) may be monitored for use in acquiring selection data to optimize CRT (e.g., set AV and/or VV delay, optimize cardiac contractility, for example, by using and/or measuring impedance first derivative dZ/dt, select pacing site, select pacing vector, lead placement, or assess pacing capture from both the electrical and mechanical points of view (e.g., electrical capture may not mean mechanical capture, and the heart sounds and impedance may assist in assessing whether the electrical stimulus captures the heart or not by looking at the mechanical information from the heart sounds and impedance), select an effective electrode vector configuration for pacing, etc.). For example, intracardiac impedance signals between two or more electrodes may be monitored for use in providing such optimization. Exemplary generalized method <b>130</b> for use in monitoring a patient's heart and/or optimizing cardiac therapy (e.g., setting device parameters, adjusting device parameters, initializing device parameters, etc.) is diagrammatically depicted in <figref idref="DRAWINGS">FIG. 4</figref>. Method <b>130</b> is intended to illustrate the general functional operation of the devices and/or systems described herein, and should not be construed as reflective of a specific form of software or hardware necessary to practice all of the methods described herein. It is believed that the particular form of software will be determined primarily by the particular system architecture employed in the device (e.g., the IMD <b>16</b>) and by the monitoring and therapy delivery methodologies employed by the device and/or system. Providing software and/or hardware to accomplish the described methods in the context of any modern IMD, given the disclosure herein, is within the abilities of one of skill in the art.

0084The method <b>130</b> of <figref idref="DRAWINGS">FIG. 4</figref> may be generally described as a data collection process, e.g., collection of measurement data based on intracardiac impedance, for use in setting one or more device parameters. For example, the method <b>130</b> may include delivering pacing therapy (e.g., CRT therapy) at a plurality of device parameters options (block <b>132</b>) (e.g., a plurality of optional AV delays, a plurality of VV delays, a plurality of electrode vector configurations, different pacing sites, different lead placements, etc. Selection data may be acquired for each option of the plurality of options (e.g., block <b>134</b>) (e.g., for each optional AV delay, for each VV delay, for each optional electrode vector configuration used to pace the heart, etc.) for at least one cardiac cycle (e.g., a plurality of cardiac cycles at the end of a respiratory cycle). For example, such selection data may include various measurements extracted from intracardiac impedance signals based on temporal fiducial points associated with at least a part of a systolic portion and/or at least a part of a diastolic portion of the cardiac cycle (e.g., temporal fiducial points determined in one or more various manners, such as with use of detected heart sounds using an acoustic sensor, with use of minimum and maximum impedance signal detection, with use of one or more algorithms applied to a physiological parameter such as R-R interval, etc.).

0085After collection or acquisition of such selection data (block <b>134</b>) for each device parameter option, the selection data may be used to set (e.g., initialize, adjust, reset, apply, etc.) one optional device parameter of the plurality of optional device parameters for delivery of therapy (block <b>136</b>) (e.g., CRT). For example, the selection data may be used in a scoring algorithm to determine which of the device parameter options would provide better CRT results than others (e.g., which device parameter would provide optimal results). For example, one or more scoring techniques will be described herein with respect to selection of an optimal AV delay (see, e.g., <figref idref="DRAWINGS">FIGS. 23-24</figref>).

0086<figref idref="DRAWINGS">FIG. 5</figref> shows one exemplary embodiment of a method <b>150</b> for acquiring selection data for one of the device parameter options (e.g., one of the selectable device parameters that may be used to optimize CRT, such as a potential AV delay that may be an optimal parameter). For example, as shown in <figref idref="DRAWINGS">FIG. 5</figref>, pacing therapy is delivered using one of the plurality of device options (block <b>152</b>) (e.g., the plurality of device parameter options may be selected, determined and/or calculated AV delays, such as percentages of intrinsic AV delay, for example, 40% of intrinsic AV delay, 50% of intrinsic AV delay, 60% of intrinsic AV delay, 70% of intrinsic AV delay, 80% of intrinsic AV delay, etc.). For the device parameter option used to pace (block <b>152</b>), selection data is acquired at each of a plurality of electrode vector configurations (e.g., intracardiac impedance is monitored over a plurality of cardiac cycles and selection data is extracted using such impedance signal). As indicated by the decision block <b>154</b>, if selection data has not been acquired from all desired electrode vector configurations, then the loop of acquiring selection data (e.g., the loop illustrated by blocks <b>158</b>, <b>160</b>, <b>162</b>, and <b>164</b>) is repeated. If selection data has been acquired from all desired electrode vector configurations, then another different device parameter option is used to deliver therapy and the method <b>150</b> of <figref idref="DRAWINGS">FIG. 5</figref> is repeated (e.g., for the different device parameter option) until selection data has been acquired for all the different device parameter options (e.g., selection data being collected at each of a plurality of electrode vector configurations for each of the different device parameter options).

0087As shown in the repeated loop of acquiring selection data for each of the desired electrode vector configurations (e.g., blocks <b>158</b>, <b>160</b>, <b>162</b>, and <b>164</b>), one of the plurality of electrode vector configurations is selected for use in acquiring selection data (block <b>158</b>). Temporal fiducial points associated with at least a part of a systolic portion of at least one cardiac cycle and/or temporal fiducial points associated with at least a part of a diastolic portion of at least one cardiac cycle for the selected electrode vector configuration are acquired (block <b>160</b>) (e.g., such as with use of heart sounds, analysis of impedance signal minimum and maximums, application of algorithms based on physiological parameters such as R-R intervals, etc.). For example, temporal fiducial points associated with the systolic and/or diastolic portions of the cardiac cycle may be acquired, temporal fiducial points associated with one or more defined segments within systolic and/or diastolic portions of the cardiac cycle may be acquired, and/or temporal fiducial points within or associated with one or more points and/or portions of a systolic and/or diastolic portion of the cardiac cycle may be acquired. Yet further, for example, temporal fiducial points associated with just the systolic portion or just the diastolic portion of the cardiac cycle may be acquired, temporal fiducial points associated with one or more defined segments within just the systolic portion or just the diastolic portion of the cardiac cycle may be acquired, and/or temporal fiducial points within or associated with one or more points and/or portions of just the systolic portion or just the diastolic portion of the cardiac cycle may be acquired. In other words, fiducial points may be acquired that are associated with either both the systolic and diastolic portions of the cardiac cycle or associated with just one of such portions of the cardiac cycle. Further, for example, such fiducial points may be representative or indicative of a measurement window and/or time period (e.g., interval, point, etc.) at or during which intracardiac impedance may be measured for use in analysis as described herein.

0088In about the same timeframe (e.g., about simultaneously with the acquired fiducial points), an intracardiac impedance signal is acquired at the selected electrode vector configuration (block <b>162</b>). With the acquired fiducial points and the acquired intracardiac impedance signal, measurements from the impedance signal are extracted based on the temporal fiducial points (block <b>164</b>) (e.g., integral of the impedance signal in a measurement window defined between fiducial points, maximum slope of impedance signal in a measurement window defined between fiducial points, time between the fiducial points, maximum impedance at a fiducial point, etc.). One or more of such measurements may be comparable to desired values for such measurements allowing for a determination of whether the measurement may indicate that the device parameter option may be an effective device parameter for optimizing therapy (e.g., a scoring algorithm may be used to determine if a device parameter option may be an optimal parameter based on whether a plurality of such measurements meet certain criteria or thresholds).

0089The measurement data for each of the device parameter options (e.g., obtained such as described in <figref idref="DRAWINGS">FIG. 5</figref>) is determined for at least one cardiac cycle. In one or more embodiments, such measurement data is acquired for a plurality of cardiac cycles. The cardiac cycles during which measurement data is acquired may be any suitable cardiac cycle. In one or more embodiments, the selected cardiac cycles during which measurement data is acquired is based on the respiratory cycle. In at least one embodiment, the measurement data is acquired during cardiac cycles occurring at the end of a respiratory cycle (e.g., proximate the end of expiration).

0090For example, <figref idref="DRAWINGS">FIG. 6</figref> is illustrative of one embodiment of an algorithm for selection of cardiac cycles during which the measurements may be made. An objective of the algorithm illustrated in <figref idref="DRAWINGS">FIG. 6</figref> is to determine a three (3) cardiac cycle measurement window at the end of expiration to allow for measurement of predefined impedance parameters (e.g., via an electrode vector configuration, such as for a particular device parameter option). <figref idref="DRAWINGS">FIG. 6</figref> depicts a measurement window acquired at the end of the respiratory cycle for a three-beat assessment of cardiac function (e.g., at particular pacing delivered using a device parameter option). The impedance signal acquired at each vector configuration for each device parameter option undergoes the three-beat analysis and selection data derived from the measurements may be used to set an optimized device parameter (e.g., the measurements may be compared within the electrode vector configuration and between other vector configurations to optimize device parameters for CRT).

0091<figref idref="DRAWINGS">FIG. 6</figref> shows an impedance signal <b>170</b> acquired over multiple cardiac cycles (e.g., box <b>172</b> showing the impedance signal <b>170</b> over a three cardiac cycle window) superimposed on multiple respiratory cycles <b>174</b> (e.g., two respiratory cycles being shown illustratively in <figref idref="DRAWINGS">FIG. 6</figref>). The respiratory cycles <b>174</b> may be monitored in any suitable manner such as described herein (e.g., monitoring of transthoracic impedance signals) to determine the end of respiration such that multiple cycles proximate the end of respiration may be selected for the measurement of data. In one embodiment as shown in <figref idref="DRAWINGS">FIG. 6</figref>, the location of cardiac cycles during which measurements are made may be determined by detecting respiratory peaks <b>176</b> and/or the time duration between such respiratory peaks <b>176</b>, and then locating a region of time in a midway region between such respiratory peaks <b>176</b> representative of the end of the respiration cycle (e.g., the end of expiration). For example, the detected duration between respiratory peaks <b>176</b> may be divided in half to locate the midway region and the impedance signal <b>170</b> over multiple cardiac cycles within or proximate to the midway region (e.g., the signal in box <b>172</b>) may be selected for use in providing measurement data (e.g., cardiac impedance parameters). One will recognize that other methods of selecting particular cardiac cycles over which the measurements are made may be used, for example, based on the respiration cycle and/or other physiological data.

0092One skilled the art will recognize that any number of device parameters may be optimized in a manner such as that described herein (e.g., AV delay, VV delay, pacing vector, pacing site, pacing vector, lead placement, assessment of pacing capture from both the electrical and mechanical points of view (e.g., electrical capture may not mean mechanical capture, and the heart sounds and impedance may assist in assessing whether the electrical stimulus captures the heart or not by looking at the mechanical information from the heart sounds and impedance), etc.) For simplicity purposes, optimization of AV delay shall be described in detail herein. However, any of the processes described herein may be used to optimize any of the other device parameters in a similar manner (e.g., the optimization of VV delay may be similar to the optimization of the AV delay).

0093For example, <figref idref="DRAWINGS">FIG. 7</figref> shows one exemplary embodiment of a method <b>180</b> for acquiring selection data for one AV delay of a plurality of selectable potential AV delays that may be used to optimize CRT. As described herein, the method <b>180</b> is repeated for each potential AV delay that may possibly be set as the optimal parameter. For example, as shown in <figref idref="DRAWINGS">FIG. 7</figref>, pacing therapy is delivered using one of a plurality of AV delays (block <b>182</b>) (e.g., the plurality of AV delays may be selected, determined and/or calculated AV delays, such as percentages of intrinsic AV delay, for example, 40% of intrinsic AV delay, 50% of intrinsic AV delay, 60% of intrinsic AV delay, 70% of intrinsic AV delay, 80% of intrinsic AV delay, etc.). The user may be allowed to set a window of allowable optional AV delays. For example, during an initial programming of the device, a user may set a parameter thereof allowing only for optional AV delays within a range, for example, 40% to 80% of intrinsic AV conduction time.

0094For a particular AV delay (e.g., a selected 40% of intrinsic AV delay) used to pace (block <b>182</b>), selection data is acquired at each of a plurality of electrode vector configurations (e.g., intracardiac impedance is monitored over a plurality of cardiac cycles and selection data is extracted using such impedance signal). As indicated by the decision block <b>184</b>, if selection data has not been acquired from all desired electrode vector configurations, then the loop of acquiring selection data is repeated (e.g., blocks <b>188</b>, <b>190</b>, <b>192</b>, and <b>194</b>). If selection data has been acquired from all desired electrode vector configurations, then another AV delay option is used to deliver therapy and the method <b>180</b> of <figref idref="DRAWINGS">FIG. 7</figref> is repeated (e.g., for a different AV delay) until selection data has been acquired for all the potential different AV delay options (e.g., selection data being collected at each of a plurality of electrode vector configurations for each of the AV delays). One will recognize that the electrode vector configuration may be set first followed by proceeding to evaluate all of the device parameter options at the particular electrode vector configuration, and then another different electrode vector configuration may be set followed by collecting measurements to evaluate all of the device parameter options at the newly set electrode vector configuration, and so forth. At least in one embodiment, measurements are made for each device parameter option at each desired electrode vector configuration.

0095As shown in the repeated loop of acquiring selection data for each of the desired electrode vector configurations (e.g., blocks <b>188</b>, <b>190</b>, <b>192</b>, and <b>194</b>), one of the plurality of electrode vector configurations is selected for use in acquiring selection data (block <b>188</b>). Temporal fiducial points associated with at least a part of a systolic portion of at least one cardiac cycle and/or temporal fiducial points associated with at least a part of a diastolic portion of the at least one cardiac cycle for the selected electrode vector configuration are acquired (block <b>190</b>) (e.g., such as with use of heart sounds, analysis of impedance signal minimum and maximums, application of algorithms based on physiological parameters such as R-R intervals, etc.). In about the same timeframe (e.g., about simultaneously with the acquired fiducial points), an intracardiac impedance signal is acquired at the selected electrode vector configuration (block <b>192</b>). With the acquired fiducial points and the acquired intracardiac impedance signal, measurements from the impedance signal are extracted based on the temporal fiducial points (block <b>194</b>) (e.g., integral of impedance signal between fiducial points, maximum slope of impedance signal between fiducial points, time between the fiducial points, etc.).

0096One or more of such measurements may be comparable to desired values for such measurements allowing for a determination of whether the measurement may indicate that the AV delay option may be an effective AV delay for optimizing therapy (e.g., CRT) (e.g., a scoring algorithm may be used to determine if an AV delay may be an optimal AV delay based on whether a plurality of such measurements meet certain criteria or thresholds). The measurement for each of the AV delay options may be acquired for one or more cardiac cycles selected, such as described with reference to <figref idref="DRAWINGS">FIG. 6</figref> (e.g., at the end of expiration in the respiratory cycle).

0097The extraction of measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based on the temporal fiducial points and associated with at least a part of the systolic portion of at least one cardiac cycle and/or associated with at least a part of the diastolic portion of the at least one cardiac cycle (e.g., selection data acquisition loop including <b>158</b>, <b>160</b>, <b>162</b>, and <b>164</b> as shown in <figref idref="DRAWINGS">FIG. 5</figref> or selection data acquisition loop including <b>188</b>, <b>190</b>, <b>192</b>, and <b>194</b> as shown in <figref idref="DRAWINGS">FIG. 7</figref>) may be implemented in one or more manners (e.g., using one or more algorithms in accordance with the functionality described herein). For example, a method to optimize AV and/or VV intervals (e.g., which are part of a collective group of CRT optimization device parameters) detects relative or absolute changes in chamber blood volume and/or chamber dimensions, isovolumic contraction and ejection times and isovolumic relaxation and filling times, based on selected measurements from impedance waveform morphologies such as a magnitude delta between impedance waveform fiducial points, a time duration between impedance waveform fiducial points, positive and negative slopes between impedance waveform fiducial points, an integral between impedance waveform fiducial points, an area between impedance waveform fiducial points, other deviations in the waveform morphology to assess hemodynamic parameters such as end diastolic volume/dimension, end systolic volume/dimension and stroke volume, isovolumic contraction and relaxation times, ejection and filling times (e.g., such as those that are conventionally measured with echocardiography methods to optimize CRT), etc.

0098For example, as described herein, one exemplary algorithm defines a method that measures defined parameters between fiducial points on intracardiac impedance waveform morphologies acquired from separate electrode vector configurations. Information acquired from each electrode vector configuration may be tabulated and an optimal AV and/or VV delay setting may be determined based on a composite scoring process from all impedance electrode vector configurations. For example, measurements acquired between impedance waveform fiducial points may include impedance minimum and maximums, time duration, integral, slope and the like to provide closed loop feedback on cardiac cycle ejection and filling periods. In this exemplary algorithm, cardiac cycle ejection encompasses isovolumic contraction and ejection, which is approximately 40% of the cardiac cycle duration whereas the remaining 60% of the cardiac cycle duration is comprised of isovolumic relaxation and diastolic filling as shown in <figref idref="DRAWINGS">FIG. 9</figref>.

0099<figref idref="DRAWINGS">FIG. 8</figref> shows one embodiment of an exemplary method <b>200</b> to extract measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based on the temporal fiducial points and associated with the systolic portion of at least one cardiac cycle and/or associated with the diastolic portion of the at least one cardiac cycle. The method <b>200</b> extracts measurements based on temporal fiducial points defined by the valve closures (e.g., measurement windows defined by heart sounds). For example, temporal fiducial points defined by heart sounds (e.g., S<b>1</b>—mitral valve closure/tricuspid valve closure and S<b>2</b> aortic valve closure/pulmonary valve closure as shown in <figref idref="DRAWINGS">FIG. 9</figref>) associated with at least a part of systolic and/or diastolic portions of at least one cardiac cycle may be acquired (block <b>202</b>) (e.g., temporal fiducial points associated with the systolic and/or diastolic portions). For example, heart sounds that may define temporal fiducial points are described in the reference, Guyton and Hall, <i>Textbook of Medical Physiology</i>, pp. 265-268 (2011 12^thEd.) which is incorporated by reference herein in its entirety.

0100About simultaneously with the acquired fiducial points, an intracardiac impedance signal is acquired at a selected electrode vector configuration (block <b>204</b>). With the acquired fiducial points and the acquired intracardiac impedance signal, measurements from the impedance signal may be extracted based on the temporal fiducial points defined by the heart sounds (block <b>206</b>).

0101<figref idref="DRAWINGS">FIG. 9</figref> shows a diagram depicting events of the cardiac cycle for the left heart. One area of interest in optimizing device parameters is the systolic ejection period between heart sounds S<b>1</b>—mitral valve closure (MVC) and S<b>2</b>—aortic valve closure (AVC) encompassing isovolumic contraction and ejection. This period occupies 40% of the cardiac cycle. Subsequently, the diastolic filling period (between heart sound S<b>2</b> and the following cardiac cycle's S<b>1</b> heart sound) occupies the remaining 60% of the cardiac cycle. In one or more embodiments, impedance waveform measurements within these two periods or the ratio derived thereof, may be used to optimize CRT.

0102Fiducial points of interest that are detectable as described herein (e.g., using acoustic sensors) include S<b>1</b> (MVC) and S<b>2</b> (AVC). These points may be associated with impedance waveform minimum and maximum points, respectively, thus encompassing the ejection or systolic portion of the cardiac cycle. Moreover, the use of heart sounds S<b>1</b> and S<b>2</b> further aid in defining the ejection portion of the cardiac cycle and may be used to determine a time interval for impedance waveform measurements. The impedance waveform maximum and thus its associated heart sound S<b>2</b> determine the end of the systolic portion of the cardiac cycle and the start of the diastolic filling portion of the cardiac cycle. Likewise, heart sound S<b>1</b> determines the end of the diastolic portion of the cardiac cycle and the start of the systolic out flow portion of the cardiac cycle. Therefore, the heart sounds S<b>1</b> and S<b>2</b> can be used to determine the time intervals for impedance waveform measurements for the systolic and/or diastolic periods of the cardiac cycle. In other words, the heart sounds S<b>1</b> and S<b>2</b> may be used as temporal fiducial points (e.g., to define a measurement window during which one or more measurements are extracted from the impedance signal, such as, for example, positive and/or negative slopes between the heart sounds S<b>1</b> and S<b>2</b> of a cardiac cycle, positive and/or negative slopes between the heart sound S<b>2</b> of a first cardiac cycle and a heart sound S<b>1</b> of a subsequent cardiac cycle, an integral of the impedance signal between heart sounds, etc.).

0103<figref idref="DRAWINGS">FIG. 10</figref> shows an embodiment of another exemplary method <b>220</b> to extract measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based on the temporal fiducial points and associated with the systolic portion of at least one cardiac cycle and/or associated with the diastolic portion of the at least one cardiac cycle. The method <b>220</b> includes acquiring an intracardiac impedance signal (block <b>222</b>) and then extracts measurements based on temporal fiducial points defined by the intracardiac impedance signal minimum and maximum (block <b>224</b>) (e.g., points of the signal associated with and/or corresponding to heart sounds S<b>1</b> and S<b>2</b>). For example, the temporal fiducial points defined by the minimum and maximum points of the intracardiac impedance signal (e.g., such as shown, for example, in <figref idref="DRAWINGS">FIG. 11</figref>, which are substantially aligned with the beginning and end of the systolic and diastolic portions of the cardiac cycle) associated with at least a part of systolic and/or diastolic portions of at least one cardiac cycle may be acquired (block <b>224</b>) (e.g., temporal fiducial points associated with the systolic and/or diastolic portions). In addition, with the acquired fiducial points and the acquired intracardiac impedance signal, measurements from the impedance signal may be extracted based on the temporal fiducial points defined thereby (block <b>226</b>).

0104The method <b>220</b> (e.g., a selection data acquisition or measurement algorithm) relies on the concept that the ejection period is primarily associated with the time duration between the impedance waveform minimum and maximum, whereas the filling period is primarily associated with the impedance waveform maximum to subsequent impedance minimum on the following cardiac cycle. Therefore, dividing the impedance waveform cardiac cycle into systolic and diastolic periods based on the impedance waveform minimum and maximum fiducial points, and measuring, for example, the time interval between the impedance waveform minimum and maximum points, the positive and negative slopes of the signal between the impedance waveform minimum and maximum points, and the integral of the signal between the impedance waveform minimum and maximum points, can be used independently or as one or more derived ratios to determine optimal CRT settings.

0105<figref idref="DRAWINGS">FIG. 11</figref> depicts a method to determine the area of the impedance waveform morphology that is primarily associated with ejection <b>230</b> and the area that is primarily associated with filling <b>232</b>. Shown in <figref idref="DRAWINGS">FIG. 11</figref> are left ventricular (LV) pressure waveform morphology (at the top of the diagram) and the associated impedance waveform morphology (at the bottom of the diagram). There is a slight time delay (At) between the impedance waveform and LV pressure minimum <b>234</b>. The method of acquiring measurements using the impedance minimums and maximums is based on the concept that the ejection period is primarily associated with the time duration between the impedance waveform minimum and maximum, whereas the filling period is primarily associated with the impedance waveform maximum to the subsequent impedance minimum on the following cardiac cycle. Measurements using the impedance signal based on the temporal fiducial points defined by the impedance minimum and maximum points, may be acquired (e.g., such as the positive slope <b>236</b> between the minimum <b>240</b> and maximum <b>242</b> of a cardiac cycle as shown in <figref idref="DRAWINGS">FIG. 11</figref>, the negative slope <b>238</b> between the maximum <b>242</b> and a subsequent impedance minimum <b>244</b> on the following cardiac cycle as shown in <figref idref="DRAWINGS">FIG. 11</figref>, a time duration between the minimum <b>244</b> and maximum <b>246</b> of a cardiac cycle (e.g., the ejection phase) as shown in <figref idref="DRAWINGS">FIG. 11</figref>, a time duration between the maximum <b>246</b> and a subsequent impedance minimum <b>248</b> (e.g., the filling phase) as shown in <figref idref="DRAWINGS">FIG. 11</figref>, a time duration between the minimum <b>244</b> and a subsequent impedance minimum <b>248</b> as shown in <figref idref="DRAWINGS">FIG. 11</figref>, an integral between the minimum <b>248</b> and maximum <b>250</b> of a cardiac cycle (e.g., the ejection phase) as shown in <figref idref="DRAWINGS">FIG. 11</figref>, an integral between the maximum <b>250</b> and a subsequent impedance minimum <b>252</b> (e.g., the filling phase) as shown in <figref idref="DRAWINGS">FIG. 11</figref>, an integral between the minimum <b>248</b> and a subsequent impedance minimum <b>252</b> as shown in <figref idref="DRAWINGS">FIG. 11</figref>, and/or any other measurement that may be quantitatively used to optimized CRT).

0106As indicated herein, detected MVC and AVC are associated with impedance waveform minimum and maximum points, respectively. As such, the use of heart sounds S<b>1</b> and S<b>2</b> may further aid in defining the ejection portion of the cardiac cycle and can be used as a validation sensor to determine a time interval for impedance waveform measurements (e.g., such as those based on minimum and maximum impedance). Likewise, impedance waveform minimum and maximum points may be used to validate time intervals associated with heart sounds.

0107<figref idref="DRAWINGS">FIG. 12</figref> shows an embodiment of yet another exemplary method <b>260</b> to extract measurements from the intracardiac impedance signal for each of the plurality of electrode vector configurations based on the temporal fiducial points and associated with the systolic portion of at least one cardiac cycle and/or associated with the diastolic portion of the at least one cardiac cycle. The method <b>260</b> extracts measurements based on temporal fiducial points defined based on the R-R interval (block <b>262</b>) (e.g., applying an algorithm to the R-R interval for defining portions representative of systolic and diastolic portions of the cardiac cycle). For example, temporal fiducial points associated with the systolic portion of at least one cardiac cycle may include at least points associated with a first predetermined portion of an R-R interval and/or the temporal fiducial points associated with the diastolic portion of the at least one cardiac cycle may include at least points associated with a second predetermined portion of the R-R interval.

0108About simultaneously with the acquired fiducial points, an intracardiac impedance signal is acquired at a selected electrode vector configuration (block <b>264</b>). With the acquired fiducial points based on the R-R interval and the acquired intracardiac impedance signal, measurements from the impedance signal may be extracted based thereon (block <b>266</b>).

0109The method described with reference to <figref idref="DRAWINGS">FIGS. 10-11</figref> may be effective for collecting data in a setting where the impedance waveform minimum and maximum are clearly defined. However, in a setting where the impedance waveform may contain multiple peaks as shown in the impedance waveform of <figref idref="DRAWINGS">FIG. 13</figref> (the waveform at the bottom), the method <b>260</b> of <figref idref="DRAWINGS">FIG. 12</figref> based on R-R interval may rather be used (e.g., an algorithm or subroutine that defines a portion of the R-R interval as the impedance waveform measurement window). For example, an R-R interval may be detected as described herein and as shown in the waveform at the top of <figref idref="DRAWINGS">FIG. 13</figref> (e.g., an intrinsic R-R interval being 0.665 seconds). Accepting that a predefined percentage of the R-R interval is associated with the systolic portion of cardiac cycle and another predefined percentage of the R-R interval is associated with the diastolic portion of the cardiac cycle, then, for example, approximately 40% of the cardiac cycle (R-R interval) may be associated with systole and the remaining 60% of the cardiac cycle may be associated with diastole. As such, the fiducial points based on the R-R interval may include points associated with a first predetermined portion of the cardiac cycle (e.g., from a minimum impedance <b>272</b> to a point <b>274</b> in the cardiac cycle determined by the set percentage, such as 40%) and points associated with a second predetermined portion of the cardiac cycle (e.g., from the point <b>274</b> in the cardiac cycle determined by the set percentage, such as 40%, to the minimum impedance <b>276</b> of the subsequent cycle).

0110<figref idref="DRAWINGS">FIG. 13</figref> depicts the method to determine ejection periods and filling periods based on a percent time of the cardiac cycle or R-wave to R-wave interval. In this example, the R-R interval is 665 milliseconds. Calculating 40% of this interval may define a systolic period of 266 milliseconds and a diastolic period of 399 milliseconds. Impedance parameters can be measured (e.g., those described above with reference to <figref idref="DRAWINGS">FIG. 10-11</figref>) between these intervals for CRT optimization (e.g., intervals <b>272</b> to <b>274</b>, <b>274</b> to <b>276</b>, and/or <b>272</b> to <b>276</b>).

0111One skilled the art will recognize that any of the methods for acquiring selection data (e.g., measurements and/or data derived from such measurements) may be used independently and/or in combination with one or more other acquisition methods. For example, the method as described with reference to <figref idref="DRAWINGS">FIGS. 12-13</figref> may be used in combination with heart sounds to define measurement window intervals established by fiducial points. Further, one or more of such acquisition methods may be used to validate one or more of the other acquisition methods described herein. For example, the data acquisition method described with reference to <figref idref="DRAWINGS">FIGS. 10-11</figref> using impedance minimums and maximums may be used to validate acquisition of fiducial points based on heart sounds. In other words, multiple combinations of such methods described herein may be used for collection or acquisition of selection data to set optimal device parameters for CRT.

0112Further, measurements extracted using the impedance signal based on the temporal fiducial points may include various measurements (e.g., positive and negative slope, integrals, etc.) usable as selection data as described herein. Selection data may be determined based upon such extracted measurements. For example, such extracted measurements may be used independently or may be used to derive one or more types of selection data therefrom (e.g., such measurements may be used to determine or calculate other useful values). For example, with reference to <figref idref="DRAWINGS">FIG. 11</figref>, an integral between the minimum <b>248</b> and maximum <b>250</b> of a cardiac cycle (e.g., the ejection phase) as shown in <figref idref="DRAWINGS">FIG. 11</figref> may be used independently as selection data or may be used to generate a ratio with the integral between the maximum <b>250</b> and a subsequent impedance minimum <b>252</b> (e.g., the filling phase). Various types of selection data may be generated as clearly shown by the more detailed exemplary process described herein with reference to <figref idref="DRAWINGS">FIGS. 15-24</figref>.

0113<figref idref="DRAWINGS">FIG. 14</figref> depicts a full cardiac cycle measurement process that may be used to further provide additional data. The method of measurement and analysis is used to determine an impedance minimum <b>280</b>, an impedance maximum <b>282</b>, and an area under the impedance curve from impedance minimum <b>280</b> to a subsequent minimum <b>284</b> and integral (not shown) between the two minimum points <b>280</b>, <b>284</b>. This analysis depiction measures parameters per cardiac cycle rather than dividing the cardiac cycle into ejection and filling segments and making measurements for the portions of the cardiac cycle.

0114The diagram of <figref idref="DRAWINGS">FIG. 14</figref> depicts a manner of evaluating the change in impedance based on the area under the curve measured from impedance waveform minimum <b>280</b> to the subsequent waveform minimum point <b>284</b>. Data shown in this example depicts the change in impedance waveform area at baseline (BL) and at the end of 4 weeks high rate pacing in dogs (HF). The data depicts impedance waveform sensitivity to change in area under the impedance curve during sub-optimal cardiac function.

0115As generally provided herein with reference to <figref idref="DRAWINGS">FIG. 4</figref>, the method <b>130</b> includes using the acquired selection data relating to each of the plurality of options of the device parameter (e.g., AV delay) to set one option of the plurality of options for delivery of CRT to the patient. Any effective method to analyze the acquired selection data (e.g., acquired for each of a plurality of optional device parameters) and select one of the optional device parameters for use in CRT may be used. For example, such selection data may include extracted measurements from the impedance signal as described herein (e.g., slopes, integrals, areas, minimums, maximums, time durations, etc.), values derived from such extracted measurements of the impedance signal (e.g., ratios, combinations, summations, algorithm calculated values using such measurements, etc.), measurements of the impedance signal relating to the entire cardiac cycle, measurements of the impedance cycle relating to the systolic portion of the cardiac cycle, measurements relating to the diastolic portion of the cardiac cycle, and/or any other values based upon the extracted measurements of the impedance signal based on the temporal fiducial points acquired in one or more manners as described herein. The selection data may be compared to baseline data, to predetermined values, to statistically established criteria, to selection data of cardiac cycles acquired during different time periods, to selection data used to establish baseline data, to known and/or theoretical values, etc., for example, in order to determine whether the device parameter option (e.g., for which such selection data was acquired as described with reference to <figref idref="DRAWINGS">FIG. 5</figref> or <figref idref="DRAWINGS">FIG. 7</figref>) would be an optimal parameter for delivering CRT.

0116The analysis of the selection data acquired for corresponding device parameter options may be compared such that a resulting optimal device parameter may be selected. For example, selection data acquired for each of a plurality of AV delays (e.g., 40% of intrinsic AV delay, 50% of intrinsic AV delay, 60% of intrinsic AV delay, and 70% of intrinsic AV delay) may be independently analyzed for each of the corresponding AV delays. Such independent analyses may then be compared to one another for selection of an optimal AV delay.

0117One process of performing such analysis and comparison may include one or more scoring techniques suitable to evaluate and select an optimal parameter. For example, one illustrative scoring process may include providing a score for each of the plurality of options of the device parameter (e.g., for each of 40% of intrinsic AV delay, 50% of intrinsic AV delay, 60% of intrinsic AV delay, and 70% of intrinsic AV delay) based on the acquired selection data (e.g., maximums, slopes, integrals, ratios, etc.) for each vector configuration. One of the plurality of options (e.g., 50% of intrinsic AV delay) may be selected based on the scores for the plurality of options of the device parameter for delivery of CRT to the patient.

0118In one or more embodiments of the scoring process, each type of selection data (e.g., maximums, slopes, integrals, ratios, etc.) may be given the same weight in the scoring process or one or more of the types of selection data may be assigned different weights dependent upon, for example, whether such type of selection data might be more accurate and/or make more contribution in determining an optimal setting. For example, selection data such as a ratio of the slope of the impedance signal during ejection to the slope of the impedance signal during filling may provide a better indicator of a more effective device parameter than just slope of the impedance signal during filling when considered independently. One will recognize that the selection data may be acquired and stored as necessary to carry out the analysis thereof and selection of an optimal device parameter.

0119The techniques described in this disclosure, including those attributed to the IMD <b>16</b>, the programmer <b>24</b>, or various constituent components, may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, embodied in programmers, such as physician or patient programmers, stimulators, image processing devices, or other devices. The term “module,” “processor,” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry.

0120Such hardware, software, and/or firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, modules, or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components.

0121When implemented in software, the functionality ascribed to the systems, devices and techniques described in this disclosure may be embodied as instructions on a computer-readable medium such as RAM, ROM, NVRAM, EEPROM, FLASH memory, magnetic data storage media, optical data storage media, or the like. The instructions may be executed by one or more processors to support one or more aspects of the functionality described in this disclosure.

0122An exemplary algorithm for AV delay optimization shall be described with reference to <figref idref="DRAWINGS">FIGS. 15-24</figref>. The algorithm includes definition and use of four sub-routines. However, clearly such functionality may be implemented in many manners and the exemplary algorithm is provided to simply illustrate the various methods described herein (e.g., extraction of measurements, scoring, etc.) for optimizing AV delay. As indicated previously, similar methods may be used for optimizing other parameters, such as V-V delay.

0123The algorithm is started (block <b>300</b>) and various selections for implementing the algorithm are made as shown in <figref idref="DRAWINGS">FIG. 15</figref>. For example, as shown in block <b>302</b>, the type of impedance vector configurations may be selected. For example, a single impedance vector configuration may be selected for use, various impedance vector configurations may be selected from a plurality of available impedance vector configurations, or all available impedance vector configurations may be selected. Such selected impedance vector configurations (e.g., defined by selected electrodes as described herein) may be used for providing the intracardiac impedance signals from which measurements may be extracted.

0124Further, for example, as shown in block <b>304</b>, one or more various types of measurement techniques may be selected. For example, one or more of the following measurement techniques relating to the impedance (Z) signal (e.g., as described with reference to <figref idref="DRAWINGS">FIGS. 8-14</figref>; based on one or more fiducial points; relating to intervals defined by fiducial points, etc.) may be selected for use in providing selection data: 1) Z_MAX−Z_MINand Area (e.g., from Z_MINto Z_MINof following cycle); 2) the Time (e.g., between fiducial points), the Slope (e.g., between Z_MINand Z_MAX, for example, see <figref idref="DRAWINGS">FIG. 11</figref>), and Integral (e.g., between Z_MINand Z_MAX, for example, see <figref idref="DRAWINGS">FIG. 11</figref>); 3) % of R-R Interval (e.g., used to provide fiducial points to establish measurement windows, for example, see <figref idref="DRAWINGS">FIGS. 12 and 13</figref>); and 4) Heart Sounds (e.g., S<b>1</b> and S<b>2</b>, see <figref idref="DRAWINGS">FIGS. 8 and 9</figref>). As shown in block <b>304</b>, any one of such measurement techniques may be selected, any one or more of such available measurement techniques may be selected (e.g., as indicated by “5) Selected”), or all of such measurement techniques may be selected (e.g., as indicated by “6) All”).

0125With such selections made, measurement of intrinsic R-R interval may be performed (block <b>306</b>) (e.g., for use in carrying out the process described, for example, with reference to <figref idref="DRAWINGS">FIGS. 12 and 13</figref>) and calculations may be performed to provide fiducial points to establish measurement windows, for example, as described with reference to <figref idref="DRAWINGS">FIGS. 12 and 13</figref> (block <b>308</b>). For example, such calculations may include establishing a systolic measurement window portion (e.g., 40% of the R-R interval) and/or a diastolic measurement window portion (e.g., 60% of the R-R interval).

0126Further, with such selections made, measurement of intrinsic AV conduction time may be performed (block <b>310</b>) (e.g., for use in determining potential AV delay pacing parameters, for example, for use in providing CRT pacing such that selection data may be collected for each of such AV delay pacing parameters, in a manner such as described with reference to <figref idref="DRAWINGS">FIG. 7</figref>). For example, calculations may be performed to provide each of the potential optimal pacing AV intervals for which selection data may be collected in an independent manner by taking certain percentages of the intrinsic A-V conduction time (block <b>312</b>), such as, for example, 20% of intrinsic AV delay, 30% of intrinsic AV delay, 40% of intrinsic AV delay, 50% of intrinsic AV delay, 60% of intrinsic AV delay, 70% of intrinsic AV delay, 80% of intrinsic AV delay, 90% of intrinsic AV delay).

0127As each of the potentially selectable pacing AV intervals have been defined (block <b>312</b>), selection data may be acquired for one of such defined pacing AV intervals by setting it or selecting it for use to deliver pacing (block <b>314</b>) and setting the one or more impedance vector configurations (block <b>316</b>) to be used for acquiring signals from which measurements may be extracted (e.g., upon which selection data may be based). As will become apparent from the description below, selection data may be acquired for each of the other defined pacing AV interval options (e.g., the calculated % values of intrinsic AV conduction) by setting each of them for use to deliver pacing and setting the one or more impedance vector configurations to be used for acquiring signals from which measurements may be extracted for each of such AV interval options, independently from the other options.

0128The process of acquiring selection data for the set AV interval (e.g., 20% of intrinsic conduction time), as shown in <figref idref="DRAWINGS">FIG. 16</figref>, may include AV pacing at the set or preset AV interval for a period of time (e.g., 20 seconds) (block <b>320</b>). At the end of such time period, a plurality of cardiac cycles are located (block <b>322</b>) (e.g., three cardiac cycles are located at the end of expiration in a respiratory cycle, such as, for example, described with reference to <figref idref="DRAWINGS">FIG. 6</figref>).

0129As shown by the decision block <b>324</b> in <figref idref="DRAWINGS">FIG. 16</figref>, if the measurement technique relating to the analysis of Z_MAX−Z_MINand Area per cardiac cycle is selected, then such parameters are measured and stored (block <b>326</b>) (e.g., such measurements may be made as described with reference to <figref idref="DRAWINGS">FIG. 14</figref>) as selection data for use in analysis to determine the optimal AV delay. If such measurement technique was not selected, then it is determined whether the measurement technique relating to the analysis of Time, Slope, and Integral per cardiac cycle was selected (block <b>328</b>).

0130Measurement and storage of such parameters, as well as others measured and stored per the algorithms described herein, is illustratively shown in <figref idref="DRAWINGS">FIGS. 23A-23C</figref>. Further, the storage of parameters derived from measured parameters is also illustrated therein (e.g., ratios calculated and stored as shown illustratively in <figref idref="DRAWINGS">FIG. 23C</figref>).

0131As shown by the decision block <b>328</b>, if the measurement technique relating to the analysis of Time, Slope, and Integral per cardiac cycle was selected, then Subroutine <b>1</b> is performed. Subroutine <b>1</b> defines a method to measure the time duration, impedance waveform slope, and impedance waveform integral using the impedance waveform minimum to maximum period as the systolic portion of the cardiac cycle and the impedance waveform maximum to subsequent minimum of the following cardiac cycle as the diastolic portion of the cardiac cycle (see, for example, <figref idref="DRAWINGS">FIG. 11</figref>). For example, as shown in <figref idref="DRAWINGS">FIG. 18</figref>, Subroutine <b>1</b> may include performing and storing the following as shown in blocks <b>501</b>-<b>506</b>: (block <b>501</b>) Measure &amp; Store Time Duration From Impedance Waveform Minimum Z_MIN1to First Maximum Z_MAX(Label=t_EJECTION); (block <b>502</b>) Measure &amp; Store Slope From Impedance Waveform Minimum Z_MIN1to First Maximum Z_MA(Label=SL_EJECTION); (block <b>503</b>) Measure &amp; Store Integral From Impedance Waveform Minimum Z_MIN1to First Maximum Z_MAX(Label=INT_EJECTION); (block <b>504</b>) Measure &amp; Store Time Duration From Impedance Waveform Maximum Z_MAXto Second Minimum Z_MIN2(Label=t_FILLING); (block <b>505</b>) Measure &amp; Store Slope From Impedance Waveform Maximum Z_MAXto Second Minimum Z_MIN2(Label=SL_FILLING); and (block <b>506</b>) Measure &amp; Store Integral From Impedance Waveform Maximum Z_MAXto Second Minimum Z_MIN2(Label=INT_FILLING).

0132As shown by the decision block <b>328</b>, if the measurement technique relating to the analysis of Time, Slope, and Integral per cardiac cycle was not selected, then it is determined whether the measurement technique relating to the analysis of a % of R-R Interval is determined (block <b>330</b>). As shown by the decision block <b>330</b>, if the measurement technique relating to the analysis of a % of R-R Interval was selected, then Subroutine <b>2</b> is performed. Subroutine <b>2</b> defines a method that may measure the impedance waveform slope and impedance waveform integral using 40% of the R-R interval as the defined period for the systolic portion of the cardiac cycle and the remaining 60% of the R-R interval as the diastolic portion of the cardiac cycle (see, for example, <figref idref="DRAWINGS">FIGS. 12 and 13</figref>). For example, as shown in <figref idref="DRAWINGS">FIG. 19</figref>, Subroutine <b>2</b> may include performing and storing the following as shown in blocks <b>510</b>-<b>513</b>: (block <b>510</b>) Measure &amp; Store Slope From Impedance Waveform Minimum Z_MIN1to 40% Time of R→R Interval (Label=SL40%_EJECTION); (block <b>511</b>) Measure &amp; Store Integral From Impedance Waveform Minimum Z_MIN1to 40% Time of R→R Interval (Label=INT40%_EJECTION); (block <b>512</b>) Measure &amp; Store Slope From Impedance Waveform 40% Time of R→R Interval to Second Minimum Z_MIN2(Label=SL60%_FILLING); and (block <b>513</b>) Measure &amp; Store Integral From Impedance Waveform 40% Time of R→R Interval to Second Minimum Z_MIN2(Label=INT60%_FILLING).

0133As shown by the decision block <b>330</b>, if the measurement technique relating to the analysis of a % of R-R Interval was not selected, then it is determined whether the measurement technique relating to the analysis using heart sounds per cardiac cycle was selected (block <b>332</b>). As shown by the decision block <b>332</b>, if the measurement technique relating to the analysis using heart sounds was selected, then Subroutine <b>3</b> is performed. Subroutine <b>3</b> defines a method to measure the impedance waveform slope and impedance waveform integral using heart sounds S<b>1</b> to S<b>2</b> as the systolic portion of the cardiac cycle and heart sounds S<b>2</b> to S<b>1</b> of the following cardiac cycle as the diastolic portion of the cardiac cycle. For example, as shown in <figref idref="DRAWINGS">FIG. 20</figref>, Subroutine <b>3</b> may include performing and storing the following as shown in blocks <b>520</b>-<b>523</b>: (block <b>520</b>) Measure &amp; Store Impedance Slope From Heart Sounds S<b>1</b> to S<b>2</b> (Label=SL_S1→S2); (block <b>521</b>) Measure &amp; Store Impedance Integral From Heart Sounds S<b>1</b> to S<b>2</b> (Label=INT_S1→S2); (block <b>522</b>) Measure &amp; Store Impedance Slope From Heart Sounds S<b>2</b> to S<b>1</b> (Label=SL_S2→S1); and (block <b>523</b>) Measure &amp; Store Impedance Integral From Heart Sounds S<b>2</b> to S<b>1</b> (Label=INT_S2-S1).

0134As shown by the decision block <b>332</b>, if the measurement technique relating to the analysis using heart sounds was not selected, or if Subroutine <b>3</b> is completed, then as shown in <figref idref="DRAWINGS">FIG. 17</figref>, it is determined as illustrated in decision block <b>340</b> whether measurements have been acquired for all the AV interval options (e.g., 20% of intrinsic AV conduction, 30% of intrinsic AV conduction, etc.). If it is determined that measurements have not been acquired for all the AV interval options (e.g., 20% of intrinsic AV conduction, 30% of intrinsic AV conduction, etc.), then another AV interval option is set (block <b>342</b>) and the measurement portion of the algorithm is repeated (e.g., Subroutines <b>1</b>-<b>3</b>). Likewise, if measurements have not been acquired for all impedance vector configurations at each of the AV interval options (e.g., 20% of intrinsic AV conduction, 30% of intrinsic AV conduction, etc.) (block <b>344</b>), then another or next impedance vector configuration is set (block <b>346</b>) and the measurement portion of the algorithm is repeated (e.g., Subroutines <b>1</b>-<b>3</b>). It will be recognized that, at least in one embodiment, optional AV intervals may be set and measurements may be collected at each of the impedance vector configurations, or, in at least one embodiment, each of the impedance vector configurations may be set and then the optional AV intervals are used for pacing to allow for acquisition of measurements. Whatever the order of making measurements, at least in one embodiment, measurements are made for each optional AV interval at each selected impedance vector configuration.

0135Following the completion of measurements at each impedance vector configuration for each of the plurality of optional AV intervals, Subroutine <b>4</b> as illustrated in <figref idref="DRAWINGS">FIGS. 21-22</figref> may be carried out (e.g., more selection data may be determined, optimal AV delay setting may be selected, etc.). For example, Subroutine <b>4</b> defines a process to calculate and tabulate impedance waveform parameters per electrode vector configuration to determine optimal CRT therapy based on independent impedance values or ratios derived thereof. The Tables shown in <figref idref="DRAWINGS">FIGS. 23A-23C</figref> show measured impedance parameters, mean±standard deviation of all measured parameters calculated over a three cardiac cycle window and the ratios of the calculated parameters based on time, slope and integral values measured during the systolic and diastolic portions of the cardiac cycle. The Table shown in <figref idref="DRAWINGS">FIG. 24</figref>, a vector optimization table, determines which AV delay setting is optimal based on a scoring algorithm, e.g., the frequency of hits for each measured parameter.

0136For example, as shown in <figref idref="DRAWINGS">FIG. 21</figref>, the mean+/−standard deviation for all measured parameters per impedance vector configuration are calculated (block <b>540</b>) and stored (e.g., as illustrated by <figref idref="DRAWINGS">FIGS. 23A-23B</figref> representative of memory storage, database configuration, etc.). Further, for example, ejection/filling ratios for all measured parameters per impedance vector configuration are calculated (block <b>542</b>) and stored (e.g., as illustrated by <figref idref="DRAWINGS">FIG. 23C</figref> representative of memory storage, database configuration, etc.) and any further completion of analysis tables is carried out (block <b>544</b>).

0137Following the completion of data gathering and storage, various types of analysis may be implemented to determine whether one of the plurality of AV delay options is to be set as the optimal AV delay for use in providing therapy. For example, as shown by decision block <b>546</b>, if Z_MAX−Z_MINand AREA (e.g., as determined as described with reference to <figref idref="DRAWINGS">FIG. 14</figref>) are at the largest Magnitude, then the impedance vector configuration used to make such measurements is flagged and the paced AV interval for which such measurements were made is set as optimal (block <b>548</b>). For example, at least in one embodiment, the AV delay is optimized after a vector configuration is selected. For example, with respect to AREA, one can calculate the sum of the AREA under each different AV delay setting for a vector configuration of a plurality of vector configurations, and then, use the summed AREA to select the vector configuration which gives the maximum summed AREA. If this is not the case, per decision block <b>546</b>, the ratio of the ejection time versus filling time is analyzed per decision block <b>550</b>.

0138For example, as shown by decision block <b>550</b>, if Ejection Time/Filling Time (e.g., a ratio determined using the impedance measurements based on systolic and diastolic representative fiducial points) is less than one at a selected ratio, then the impedance vector configuration used to make such measurements is flagged and the paced AV interval for which such measurements were made is set as optimal (block <b>560</b>). If this is not the case, the ratio of the ejection slope versus filling slope is analyzed per decision block <b>562</b>.

0139For example, as shown by decision block <b>562</b>, if Ejection Slope/Filling Slope (e.g., a ratio determined using the impedance measurements based on systolic and diastolic representative fiducial points) is less than one at a selected ratio, then the impedance vector configuration used to make such measurements is flagged and the paced AV interval for which such measurements were made is set as optimal (block <b>564</b>). If this is not the case, per decision block <b>562</b>, the ratio of the ejection integral versus filling integral is analyzed per decision block <b>566</b>.

0140For example, as shown by decision block <b>566</b>, if Ejection Integral/Filling Integral (e.g., a ratio determined using the impedance measurements based on systolic and diastolic representative fiducial points) is less than one at a selected ratio, then the impedance vector configuration used to make such measurements is flagged and the paced AV interval for which such measurements were made is set as optimal (block <b>568</b>). If this is not the case, per decision block <b>566</b>, then a vector optimization table per electrode vector configuration (e.g., such as shown in <figref idref="DRAWINGS">FIG. 24</figref>) is completed for further analysis.

0141For example, one illustrative vector optimization table for a particular vector shown in <figref idref="DRAWINGS">FIG. 24</figref> includes a listing of various types of selection data in the left-hand column. Such data may be analyzed for each of the optional paced AV intervals (e.g., % of intrinsic AV conduction time), for example, by comparison to thresholds, comparison to one another, comparison from cycle to cycle, etc., to determine which of the optional AV intervals would be more effective than the corresponding to 60% of the intrinsic AV conduction time is indicated as scoring a hit, as shown for the Value of SL_EJECTION, the optional AV delay corresponding to 70% of the intrinsic AV conduction time is indicated as scoring a hit, etc. Further, as shown in <figref idref="DRAWINGS">FIG. 24</figref>, the most scored hits resulted for the paced AV delay corresponding to 70% of the intrinsic AV conduction time. As such, in this particular scoring embodiment, the paced AV delay corresponding to 70% of the intrinsic AV conduction time is set as the optimal AV delay for therapy.

0142Although the embodiment shown in <figref idref="DRAWINGS">FIG. 24</figref> exemplifies that the optional AV delay selected as optimal is the AV delay having the most scored hits, it will be recognized that various scoring processes may be utilized (e.g., a weighted process may be used). For example, one or more of the scored hits for the AV delay corresponding to 60% of the intrinsic AV conduction time may be given different weight than those scored hits for the paced AV delay corresponding to 70% of the intrinsic AV conduction time; resulting in a higher weighted hit score for the AV delay corresponding to the 60% of intrinsic AV conduction as opposed to the 70% of intrinsic AV conduction time. In other words, such a weighted hit score would result in the selection of the paced AV delay corresponding to 60% of the intrinsic AV conduction time as opposed to 70%. Various weighting techniques may be used. For example, currently, in <figref idref="DRAWINGS">FIG. 24</figref> no weight is applied (i.e., each hit is equally weighted by one (1)). For example, in <figref idref="DRAWINGS">FIG. 14</figref>, all the different parameters, such as, Z_MAX, Z_MIN, Z_MAX−Z_MIN, AREA, etc. has the same weight (e.g., which is one (1)). As such, in the Table of <figref idref="DRAWINGS">FIG. 24</figref>, 70% of Intrinsic AV has 15 hits since the weight for every parameter is 1, so the weighted hit is still 15, similarly 60% of intrinsic AV has weighted hit 7, and 50% of intrinsic AV has weighted hit 2. As such, the optimal setting is 70% of Intrinsic AV. However, in at least one embodiment, which may be more representative of reality, each parameter might perform differently in optimizing AV delay. Each parameter might be given different weights while calculating the final weighted hit. For instance, AREA might be given weight as 5, INT_EJECTIONmight be given weight as 4, t_EJECTION/t_FILLINGmight be given weight as 3, however, Z_MAXmight be given weight as 0.5, and Z_MINmight be given weight as 0.5 as well, SL_FILLINGhas a weight 2; this way, if the weighted hit is recalculated, one will get 14 weighted hit for 70% of intrinsic AV, 16 weighted hit for 60% of AV, 3 weighted hit for 50% of AV. As such, the optimal setting is rather 60% of intrinsic AV and not 70% of intrinsic AV.

0143In one or more embodiments, generally, impedance values of the electric path may define a periodic function, e.g., waveform, the period of which may be correlated with the cardiac cycle, or portions thereof and heart rate of the patient, in much the same manner that a cardiovascular pressure waveform defines a periodic function or portion contained within the periodic function. For example, the device implementing the processes described herein may compare an impedance, slope, area, integral or time duration of a first period to an impedance parameter of a subsequent period. The device may also compare a range (corresponding to the difference between the waveform maximum and the waveform minimum) of a first period to a range of a subsequent period. In any case, the device may determine whether the hemodynamic status of the patient has changed based on such comparisons between periods during the day, night, or circadian rhythms and optimize CRT based on input from all measurement time periods.

0144As described herein, successful implementation of CRT may require that the AV and VV delay be optimized. Optimizing AV and VV delay has been done with various sensing mechanisms such as EGM, arterial blood pressure, cutaneous impedance etc., and subsequently compared to the standard echocardiography optimization method. However, echocardiography optimization methods for CRT are often subjective and show high intra- and inter-individual variability. As such, one or more embodiments herein address this problem by measuring hemodynamic parameters with the implanted device using a single sensor to sense intracardiac impedance and another sensor to sense heart sound data. The heart sound data may be used to confirm a window time period for data to be extracted from an impedance signal based on the theory that the ejection period is primarily associated with the time between the impedance waveform minimum and maximum points, while the filling period is primarily associated with the impedance waveform maximum to a subsequent impedance minimum point on the following cardiac cycle. For example, dividing the impedance waveform into systolic and diastolic periods based on minimum and maximum points or time intervals between these points based on the % of the R-R interval, and then validating the measurement window by heart sounds S<b>1</b> and S<b>2</b>, may be useful in defining systole and diastole. For example, <figref idref="DRAWINGS">FIG. 24</figref> includes an exemplary table that shows that the optimal AV conduction time is chosen by the maximum number of parameter hits obtained for each intrinsic AV delay. Each parameter is calculated using the data extracted from the intracardiac impedance data and then a check mark is placed in the optimal intrinsic AV delay column. Additionally, each parameter can be accorded a different weight.

0145One or more of the following steps and/or features may be included in a medical device and/or an implantable medical device method: (a) acquiring heart sounds S<b>1</b> and S<b>2</b> from an electrode; (b) acquiring, about simultaneously with the heart sounds S<b>1</b> and S<b>2</b>, an intracardiac impedance signal from a first electrode vector configuration; (c) extracting intracardiac impedance data between fiducial points on the intracardiac impedance signal; (d) associating each parameter with an optimal conduction time from a set of conduction times; (e) determining a maximum number of parameters are optimally associated with a conduction time from the set of conduction times; (f) assigning an effectiveness score to the first electrode vector configuration in response to step (e); (g) repeating steps (a)-(f) for a second electrode vector configuration; and (h) selecting one of the first and the second electrode vector configuration based upon their respective effectiveness score. For example, in one or more embodiments, the conduction time may be associated with one of an A-V delay and a V-V delay; the effectiveness score may be associated with one of an A-V delay and a V-V delay; the impedance fiducial points may include MVC and AVC, each of which are associated with impedance waveform minimum and maximum points, respectively; S<b>1</b> and S<b>2</b> may verify an ejection portion of a first cardiac cycle and a time interval for extracting impedance waveform measurements from the first and second intracardiac impedance signals; the impedance waveform maximum to a subsequent impedance waveform minimum and its associated subsequent heart sound S<b>1</b> may determine the time interval for impedance waveform measurement for a diastolic period of the cardiac cycle while the impedance waveform minimum and its associated subsequent heart sound S<b>2</b> may determine an end of a systolic portion of the cardiac cycle and a start of the diastolic filling portion of the cardiac cycle.

0146All patents, patent documents, and references cited herein are incorporated in their entirety as if each were incorporated separately. This disclosure has been provided with reference to illustrative embodiments and is not meant to be construed in a limiting sense. As described previously, one skilled in the art will recognize that other various illustrative applications may use the techniques as described herein to take advantage of the beneficial characteristics of the apparatus and methods described herein. Various modifications of the illustrative embodiments, as well as additional embodiments of the disclosure, will be apparent upon reference to this description.